Cellular and Molecular Life Sciences

, Volume 72, Issue 18, pp 3457–3488 | Cite as

The short and long of noncoding sequences in the control of vascular cell phenotypes

Review

Abstract

The two principal cell types of importance for normal vessel wall physiology are smooth muscle cells and endothelial cells. Much progress has been made over the past 20 years in the discovery and function of transcription factors that coordinate proper differentiation of these cells and the maintenance of vascular homeostasis. More recently, the converging fields of bioinformatics, genomics, and next generation sequencing have accelerated discoveries in a number of classes of noncoding sequences, including transcription factor binding sites (TFBS), microRNA genes, and long noncoding RNA genes, each of which mediates vascular cell differentiation through a variety of mechanisms. Alterations in the nucleotide sequence of key TFBS or deviations in transcription of noncoding RNA genes likely have adverse effects on normal vascular cell phenotype and function. Here, the subject of noncoding sequences that influence smooth muscle cell or endothelial cell phenotype will be summarized as will future directions to further advance our understanding of the increasingly complex molecular circuitry governing normal vascular cell differentiation and how such information might be harnessed to combat vascular diseases.

Keywords

microRNA Long noncoding RNA Transcription factor binding site Smooth muscle cell Endothelial cell Differentiation 

Abbreviations

CRISPR

Clustered regularly interspaced short palindromic repeats

EC

Endothelial cell

ENCODE

Encyclopedia of DNA Elements

ETS

E26 transformation specific

LncRNA

Long noncoding RNA

LSS

Laminar shear stress

Mir

MicroRNA

MYOCD

Myocardin

NAT

Natural antisense transcript

NICD

Notch intracellular domain

RACE

Rapid amplification of cDNA ends

SMC

Smooth muscle cell

SNP

Single nucleotide polymorphism

SRF

Serum response factor

TFBS

Transcription factor binding site

Notes

Acknowledgments

Work in the Miano lab is supported by National Institutes of Health grants HL-117907 and HL-112793. Work in the Long lab is supported by National Institutes of Health grant HL-112686 and a Scientist Development Grant from the American Heart Association (3670036). The authors apologize to those authors whose important work was not cited due to space constraints.

References

  1. 1.
    Owens GK, Kumar MS, Wamhoff BR (2004) Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev 84(3):767–801PubMedGoogle Scholar
  2. 2.
    Naik V, Leaf EM, Hu JH, Yang HY, Nguyen NB, Giachelli CM, Speer MY (2012) Sources of cells that contribute to atherosclerotic intimal calcification: an in vivo genetic fate mapping study. Cardiovasc Res 94(3):545–554. doi: 10.1093/cvr/cvs126 PubMedCentralPubMedGoogle Scholar
  3. 3.
    Feil S, Fehrenbacher B, Lukowski R, Essmann F, Schulze-Osthoff K, Schaller M, Feil R (2014) Transdifferentiation of vascular smooth muscle cells to macrophage-like cells during atherogenesis. Circ Res 115(7):662–667. doi: 10.1161/CIRCRESAHA.115.304634 PubMedGoogle Scholar
  4. 4.
    Tang Z, Wang A, Yuan F, Yan Z, Liu B, Chu JS, Helms JA, Li S (2012) Differentiation of multipotent vascular stem cells contributes to vascular diseases. Nat Commun 3:875PubMedGoogle Scholar
  5. 5.
    Kennedy E, Mooney CJ, Hakimjavadi R, Fitzpatrick E, Guha S, Collins LE, Loscher CE, Morrow D, Redmond EM, Cahill PA (2014) Adult vascular smooth muscle cells in culture express neural stem cell markers typical of resident multipotent vascular stem cells. Cell Tissue Res 358(1):203–216. doi: 10.1007/s00441-014-1937-2 PubMedGoogle Scholar
  6. 6.
    Nemenoff RA, Horita H, Ostriker AC, Furgeson SB, Simpson PA, VanPutten V, Crossno J, Offermanns S, Weiser-Evans MC (2011) SDF-1alpha induction in mature smooth muscle cells by inactivation of PTEN is a critical mediator of exacerbated injury-induced neointima formation. Arterioscler Thromb Vasc Biol 31(6):1300–1308. doi: 10.1161/ATVBAHA.111.223701 PubMedCentralPubMedGoogle Scholar
  7. 7.
    Nguyen AT, Gomez D, Bell RD, Campbell JH, Clowes AW, Gabbiani G, Giachelli CM, Parmacek MS, Raines EW, Rusch NJ, Speer MY, Sturek M, Thyberg J, Towler DA, Weiser-Evans MC, Yan C, Miano JM, Owens GK (2013) Smooth muscle cell plasticity: fact or fiction? Circ Res 112(1):17–22PubMedCentralPubMedGoogle Scholar
  8. 8.
    Herring BP, Hoggatt AM, Burlak C, Offermanns S (2014) Previously differentiated medial vascular smooth muscle cells contribute to neointima formation following vascular injury. Vascular Cell 6:21. doi: 10.1186/2045-824X-6-21 PubMedCentralPubMedGoogle Scholar
  9. 9.
    Davies PF, Civelek M, Fang Y, Fleming I (2013) The atherosusceptible endothelium: endothelial phenotypes in complex haemodynamic shear stress regions in vivo. Cardiovasc Res 99(2):315–327. doi: 10.1093/cvr/cvt101 PubMedCentralPubMedGoogle Scholar
  10. 10.
    ENCODE Project Consortium (2004) The ENCODE (ENCyclopedia Of DNA Elements) Project. Science 306:636–640Google Scholar
  11. 11.
    ENCODE Project Consortium (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799–816Google Scholar
  12. 12.
    ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489(7414):57–74Google Scholar
  13. 13.
    Kellis M, Wold B, Snyder MP, Bernstein BE, Kundaje A, Marinov GK, Ward LD, Birney E, Crawford GE, Dekker J, Dunham I, Elnitski LL, Farnham PJ, Feingold EA, Gerstein M, Giddings MC, Gilbert DM, Gingeras TR, Green ED, Guigo R, Hubbard T, Kent J, Lieb JD, Myers RM, Pazin MJ, Ren B, Stamatoyannopoulos JA, Weng Z, White KP, Hardison RC (2014) Defining functional DNA elements in the human genome. Proc Natl Acad Sci USA 111(17):6131–6138. doi: 10.1073/pnas.1318948111 PubMedCentralPubMedGoogle Scholar
  14. 14.
    Ohno S (1972) So much “junk” DNA in our genome. Brookhaven Symp Biol 23:366–370PubMedGoogle Scholar
  15. 15.
    Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermuller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316(5830):1484–1488PubMedGoogle Scholar
  16. 16.
    Gerstein MB, Kundaje A, Hariharan M, Landt SG, Yan KK, Cheng C, Mu XJ, Khurana E, Rozowsky J, Alexander R, Min R, Alves P, Abyzov A, Addleman N, Bhardwaj N, Boyle AP, Cayting P, Charos A, Chen DZ, Cheng Y, Clarke D, Eastman C, Euskirchen G, Frietze S, Fu Y, Gertz J, Grubert F, Harmanci A, Jain P, Kasowski M, Lacroute P, Leng J, Lian J, Monahan H, O’Geen H, Ouyang Z, Partridge EC, Patacsil D, Pauli F, Raha D, Ramirez L, Reddy TE, Reed B, Shi M, Slifer T, Wang J, Wu L, Yang X, Yip KY, Zilberman-Schapira G, Batzoglou S, Sidow A, Farnham PJ, Myers RM, Weissman SM, Snyder M (2012) Architecture of the human regulatory network derived from ENCODE data. Nature 489(7414):91–100PubMedCentralPubMedGoogle Scholar
  17. 17.
    Neph S, Vierstra J, Stergachis AB, Reynolds AP, Haugen E, Vernot B, Thurman RE, John S, Sandstrom R, Johnson AK, Maurano MT, Humbert R, Rynes E, Wang H, Vong S, Lee K, Bates D, Diegel M, Roach V, Dunn D, Neri J, Schafer A, Hansen RS, Kutyavin T, Giste E, Weaver M, Canfield T, Sabo P, Zhang M, Balasundaram G, Byron R, MacCoss MJ, Akey JM, Bender MA, Groudine M, Kaul R, Stamatoyannopoulos JA (2012) An expansive human regulatory lexicon encoded in transcription factor footprints. Nature 489(7414):83–90PubMedCentralPubMedGoogle Scholar
  18. 18.
    Vaquerizas JM, Kummerfeld SK, Teichmann SA, Luscombe NM (2009) A census of human transcription factors: function, expression and evolution. Nat Rev Genet 10(4):252–263PubMedGoogle Scholar
  19. 19.
    Majesky MW (2007) Developmental basis of vascular smooth muscle diversity. Arterioscler Thromb Vasc Biol 27(6):1248–1258PubMedGoogle Scholar
  20. 20.
    Treisman R (1986) Identification of a protein-binding site that mediates transcriptional response of the c-fos gene to serum factors. Cell 46:567–574PubMedGoogle Scholar
  21. 21.
    Minty A, Kedes L (1986) Upstream regions of the human cardiac actin gene that modulate its transcription in muscle cells: presence of an evolutionarily conserved repeated motif. Mol Cell Biol 6(6):2125–2136PubMedCentralPubMedGoogle Scholar
  22. 22.
    Norman C, Runswick M, Pollock R, Treisman R (1988) Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element. Cell 55(6):989–1003PubMedGoogle Scholar
  23. 23.
    Miano JM (2010) Role of serum response factor in the pathogenesis of disease. Lab Invest 90(9):1274–1284PubMedGoogle Scholar
  24. 24.
    Miano JM, Long X, Fujiwara K (2007) Serum response factor: master regulator of the actin cytoskeleton and contractile apparatus. Am J Physiol Cell Physiol 292:C70–C81PubMedGoogle Scholar
  25. 25.
    Sun Q, Chen G, Streb JW, Long X, Yang Y, Stoeckert CJ Jr, Miano JM (2006) Defining the mammalian CArGome. Genome Res 16:197–207PubMedCentralPubMedGoogle Scholar
  26. 26.
    Benson CC, Zhou Q, Long X, Miano JM (2011) Identifying functional single nucleotide polymorphisms in the human CArGome. Physiol Genomics 43:1038–1048PubMedCentralPubMedGoogle Scholar
  27. 27.
    Li L, Liu ZC, Mercer B, Overbeek P, Olson EN (1997) Evidence for serum response factor-mediated regulatory networks governing SM22α transcription in smooth, skeletal, and cardiac muscle cells. Dev Biol 187:311–321PubMedGoogle Scholar
  28. 28.
    Mack CP, Owens GK (1999) Regulation of smooth muscle α-actin expression in vivo is dependent on CArG elements within the 5′ and first intron promoter regions. Circ Res 84:852–861PubMedGoogle Scholar
  29. 29.
    Touw K, Hoggatt AM, Simon G, Herring BP (2007) Hprt -targeted transgenes provide new insight into smooth muscle-restricted promoter activity. Am J Physiol Cell Physiol 292:C1024–C1032PubMedGoogle Scholar
  30. 30.
    Manabe I, Owens GK (2001) CArG elements control smooth muscle subtype-specific expression of smooth muscle myosin in vivo. J Clin Invest 107:823–834PubMedCentralPubMedGoogle Scholar
  31. 31.
    Lilly B, Olson EN, Beckerle MC (2001) Identification of a CArG box-dependent enhancer within the cysteine-rich protein 1 gene that directs expression in arterial but not venous or visceral smooth muscle cells. Dev Biol 240:531–547PubMedGoogle Scholar
  32. 32.
    Long X, Tharp DL, Georger MA, Slivano OJ, Lee MY, Wamhoff BR, Bowles DK, Miano JM (2009) The smooth muscle cell-restricted KCNMB1 ion channel subunit is a direct transcriptional target of serum response factor and myocardin. J Biol Chem 284(48):33671–33682PubMedCentralPubMedGoogle Scholar
  33. 33.
    Long X, Slivano OJ, Cowan SL, Georger MA, Lee TH, Miano JM (2011) Smooth muscle calponin: an unconventional CArG-dependent gene that antagonizes neointimal formation. Arterioscler Thromb Vasc Biol 31(10):2172–2180PubMedCentralPubMedGoogle Scholar
  34. 34.
    Nanda V, Miano JM (2012) Leiomodin 1: a new serum response factor-dependent target gene expressed preferentially in differentiated smooth muscle cells. J Biol Chem 287(4):2459–2467PubMedCentralPubMedGoogle Scholar
  35. 35.
    Miano JM, Ramanan N, Georger MA, de Mesy-Bentley KL, Emerson RL, Balza RO Jr, Xiao Q, Weiler H, Ginty DD, Misra RP (2004) Restricted inactivation of serum response factor to the cardiovascular system. Proc Natl Acad Sci USA 101(49):17132–17137PubMedCentralPubMedGoogle Scholar
  36. 36.
    Wirth A, Benyo Z, Lukasova M, Leutgeb B, Wettschureck N, Gorbey S, Orsy P, Horvath B, Maser-Gluth C, Greiner E, Lemmer B, Schutz G, Gutkind JS, Offermanns S (2008) G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension. Nat Med 14(1):64–68PubMedGoogle Scholar
  37. 37.
    Cooper SJ, Trinklein ND, Nguyen L, Myers RM (2007) Serum response factor binding sites differ in three human cell types. Genome Res 17(2):136–144PubMedCentralPubMedGoogle Scholar
  38. 38.
    Valouev A, Johnson DS, Sundquist A, Medina C, Anton E, Batzoglou S, Myers RM, Sidow A (2008) Genome-wide analysis of transcription factor binding sites based on ChIP-Seq data. Nat Methods 5(9):829–834PubMedCentralPubMedGoogle Scholar
  39. 39.
    Sullivan AL, Benner C, Heinz S, Huang W, Xie L, Miano JM, Glass CK (2011) SRF utilizes distinct promoter and enhancer-based mechanisms to regulate cytoskeletal gene expression in macrophages. Mol Cell Biol 31(4):861–875PubMedCentralPubMedGoogle Scholar
  40. 40.
    Zhang SX, Gras EG, Wycuff DR, Marriot SJ, Kadeer N, Yu W, Olson EN, Garry DJ, Parmacek MS, Schwartz RJ (2005) Identification of direct serum response factor gene targets during DMSO induced P19 cardiac cell differentiation. J Biol Chem 280(19):19115–19126PubMedGoogle Scholar
  41. 41.
    Garrido-Martin EM, Blanco FJ, Roque M, Novensa L, Tarocchi M, Lang UE, Suzuki T, Friedman SL, Botella LM, Bernabeu C (2013) Vascular injury triggers kruppel-like factor 6 mobilization and cooperation with specificity protein 1 to promote endothelial activation through upregulation of the activin receptor-like kinase 1 gene. Circ Res 112(1):113–127PubMedCentralPubMedGoogle Scholar
  42. 42.
    Lupski JR, Belmont JW, Boerwinkle E, Gibbs RA (2011) Clan genomics and the complex architecture of human disease. Cell 147(1):32–43PubMedCentralPubMedGoogle Scholar
  43. 43.
    Esnault C, Stewart A, Gualdrini F, East P, Horswell S, Matthews N, Treisman R (2014) Rho-actin signaling to the MRTF coactivators dominates the immediate transcriptional response to serum in fibroblasts. Genes Dev 28(9):943–958. doi: 10.1101/gad.239327.114 PubMedCentralPubMedGoogle Scholar
  44. 44.
    Dekker J, Rippe K, Dekker M, Kleckner N (2002) Capturing chromosome conformation. Science 295(5558):1306–1311PubMedGoogle Scholar
  45. 45.
    Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339(6121):819–823. doi: 10.1126/science.1231143 PubMedCentralPubMedGoogle Scholar
  46. 46.
    Han Y, Slivano OJ, Christie CK, Cheng AW, Miano JM (2015) CRISPR-Cas9 genome editing of a single regulatory element nearly abolishes target gene expression in mice. Arterioscler Thromb Vasc Biol 35:312–315. doi: 10.1161/ATVBAHA.114.305017 PubMedGoogle Scholar
  47. 47.
    Sun Q, Taurin S, Sethakorn N, Long X, Imamura M, Wang DZ, Zimmer WE, Dulin NO, Miano JM (2009) Myocardin-dependent activation of the CArG box-rich smooth muscle gamma actin gene: Preferential utilization of a single CArG element through functional association with the NKX3.1 homeodomain protein. J Biol Chem 284(47):32582–32590PubMedCentralPubMedGoogle Scholar
  48. 48.
    Wang DZ, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, Krieg PA, Olson EN (2001) Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor. Cell 105(7):851–862PubMedGoogle Scholar
  49. 49.
    Nam YJ, Song K, Luo X, Daniel E, Lambeth K, West K, Hill JA, DiMaio JM, Baker LA, Bassel-Duby R, Olson EN (2013) Reprogramming of human fibroblasts toward a cardiac fate. Proc Natl Acad Sci USA 110(14):5588–5593. doi: 10.1073/pnas.1301019110 PubMedCentralPubMedGoogle Scholar
  50. 50.
    Chen J, Kitchen CM, Streb JW, Miano JM (2002) Myocardin: a component of a molecular switch for smooth muscle differentiation. J Mol Cell Cardiol 34(10):1345–1356PubMedGoogle Scholar
  51. 51.
    Wang Z, Wang DZ, Pipes GCT, Olson EN (2003) Myocardin is a master regulator of smooth muscle gene expression. Proc Natl Acad Sci USA 100(12):7129–7134PubMedCentralPubMedGoogle Scholar
  52. 52.
    Long X, Bell RD, Gerthoffer WT, Zlokovic BV, Miano JM (2008) Myocardin is sufficient for a SMC-like contractile phenotype. Arterioscler Thromb Vasc Biol 28(8):1505–1510PubMedCentralPubMedGoogle Scholar
  53. 53.
    Raphel L, Talasila A, Cheung C, Sinha S (2012) Myocardin overexpression is sufficient for promoting the development of a mature smooth muscle cell-like phenotype from human embryonic stem cells. PLoS One 7(8):e44052. doi: 10.1371/journal.pone.0044052 PubMedCentralPubMedGoogle Scholar
  54. 54.
    Yoshida T, Kawai-Kowase K, Owens GK (2004) Forced expression of myocardin is not sufficient for induction of smooth muscle differentiation in multipotential cells. Arterioscler Thromb Vasc Biol 24(9):1596–1601PubMedGoogle Scholar
  55. 55.
    Kitchen CM, Cowan SL, Long X, Miano JM (2013) Expression and promoter analysis of a highly restricted integrin alpha gene in vascular smooth muscle. Gene 513(1):82–89PubMedCentralPubMedGoogle Scholar
  56. 56.
    Parmacek MS (2008) Myocardin: dominant driver of the smooth muscle cell contractile phenotype. Arterioscler Thromb Vasc Biol 28(8):1416–1417. doi: 10.1161/ATVBAHA.108.168930 PubMedCentralPubMedGoogle Scholar
  57. 57.
    Boucher J, Gridley T, Liaw L (2012) Molecular pathways of notch signaling in vascular smooth muscle cells. Front Physiol 3:81PubMedCentralPubMedGoogle Scholar
  58. 58.
    Iso T, Hamamori Y, Kedes L (2003) Notch signaling in vascular development. Arterioscler Thromb Vasc Biol 23:543–553PubMedGoogle Scholar
  59. 59.
    Castel D, Mourikis P, Bartels SJ, Brinkman AB, Tajbakhsh S, Stunnenberg HG (2013) Dynamic binding of RBPJ is determined by Notch signaling status. Genes Dev 27(9):1059–1071. doi: 10.1101/gad.211912.112 PubMedCentralPubMedGoogle Scholar
  60. 60.
    Noseda M, Fu Y, Niessen K, Wong F, Chang L, McLean G, Karsan A (2006) Smooth muscle alpha-actin is a direct target of Notch/CSL. Circ Res 98(12):1468–1470. doi: 10.1161/01.RES.0000229683.81357.26 PubMedGoogle Scholar
  61. 61.
    Doi H, Iso T, Sato H, Yamazaki M, Matsui H, Tanaka T, Manabe I, Arai M, Nagai R, Kurabayashi M (2006) Jagged1-selective notch signaling induces smooth muscle differentiation via RBP-J k-dependent pathway. J Biol Chem 281(39):28555–28564PubMedGoogle Scholar
  62. 62.
    Boucher JM, Peterson SM, Urs S, Zhang C, Liaw L (2011) The miR-143/145 cluster is a novel transcriptional target of Jagged-1/Notch signaling in vascular smooth muscle cells. J Biol Chem 286(32):28312–28321PubMedCentralPubMedGoogle Scholar
  63. 63.
    Rensen SSM, Niessen PM, Long X, Doevendans PA, Miano JM, van Eys GJJM (2006) Contribution of serum response factor and myocardin to transcriptional regulation of smoothelins. Cardiovasc Res 70:136–145PubMedGoogle Scholar
  64. 64.
    Briot A, Jaroszewicz A, Warren CM, Lu J, Touma M, Rudat C, Hofmann JJ, Airik R, Weinmaster G, Lyons K, Wang Y, Kispert A, Pellegrini M, Iruela-Arispe ML (2014) Repression of Sox9 by Jag1 is continuously required to suppress the default chondrogenic fate of vascular smooth muscle cells. Dev Cell 31(6):707–721. doi: 10.1016/j.devcel.2014.11.023 PubMedGoogle Scholar
  65. 65.
    Long X, Creemers EE, Wang DZ, Olson EN, Miano JM (2007) Myocardin is a bifunctional switch for smooth versus skeletal muscle differentiation. Proc Natl Acad Sci USA 104(42):16570–16575PubMedCentralPubMedGoogle Scholar
  66. 66.
    Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425(6958):577–584PubMedGoogle Scholar
  67. 67.
    Black BL, Olson EN (1998) Transcriptional control of muscle development by myocyte enhancer factor-2 (MEF2) proteins. Annu Rev Cell Dev Biol 14:167–196PubMedGoogle Scholar
  68. 68.
    Mao X, Debenedittis P, Sun Y, Chen J, Yuan K, Jiao K, Chen Y (2012) Vascular smooth muscle cell Smad4 gene is important for mouse vascular development. Arterioscler Thromb Vasc Biol 32(9):2171–2177. doi: 10.1161/ATVBAHA.112.253872 PubMedCentralPubMedGoogle Scholar
  69. 69.
    Lin Q, Lu J, Yanagisawa H, Webb R, Lyons GE, Richardson JA, Olson EN (1998) Requirement of the MADS-box transcription factor MEF2C for vascular development. Development 125(22):4565–4574PubMedGoogle Scholar
  70. 70.
    Pollock R, Treisman R (1991) Human SRF-related proteins: DNA-binding properties and potential regulatory targets. Genes Dev 5:2327–2341PubMedGoogle Scholar
  71. 71.
    Claussnitzer M, Dankel SN, Klocke B, Grallert H, Glunk V, Berulava T, Lee H, Oskolkov N, Fadista J, Ehlers K, Wahl S, Hoffmann C, Qian K, Ronn T, Riess H, Muller-Nurasyid M, Bretschneider N, Schroeder T, Skurk T, Horsthemke B, Diagram+Consortium, Spieler D, Klingenspor M, Seifert M, Kern MJ, Mejhert N, Dahlman I, Hansson O, Hauck SM, Bluher M, Arner P, Groop L, Illig T, Suhre K, Hsu YH, Mellgren G, Hauner H, Laumen H (2014) Leveraging cross-species transcription factor binding site patterns: from diabetes risk loci to disease mechanisms. Cell 156(1-2):343–358. doi: 10.1016/j.cell.2013.10.058 PubMedGoogle Scholar
  72. 72.
    Park C, Kim TM, Malik AB (2013) Transcriptional regulation of endothelial cell and vascular development. Circ Res 112(10):1380–1400. doi: 10.1161/CIRCRESAHA.113.301078 PubMedCentralPubMedGoogle Scholar
  73. 73.
    Nishikawa SI (2001) A complex linkage in the developmental pathway of endothelial cell and hematopoietic cells. Curr Opin Cell Biol 13:673–678PubMedGoogle Scholar
  74. 74.
    Li J, Huang NF, Zou J, Laurent TJ, Lee JC, Okogbaa J, Cooke JP, Ding S (2013) Conversion of human fibroblasts to functional endothelial cells by defined factors. Arterioscler Thromb Vasc Biol 33(6):1366–1375. doi: 10.1161/ATVBAHA.112.301167 PubMedCentralPubMedGoogle Scholar
  75. 75.
    Margariti A, Winkler B, Karamariti E, Zampetaki A, Tsai TN, Baban D, Ragoussis J, Huang Y, Han JD, Zeng L, Hu Y, Xu Q (2012) Direct reprogramming of fibroblasts into endothelial cells capable of angiogenesis and reendothelialization in tissue-engineered vessels. Proc Natl Acad Sci USA 109(34):13793–13798. doi: 10.1073/pnas.1205526109 PubMedCentralPubMedGoogle Scholar
  76. 76.
    Ginsberg M, James D, Ding BS, Nolan D, Geng F, Butler JM, Schachterle W, Pulijaal VR, Mathew S, Chasen ST, Xiang J, Rosenwaks Z, Shido K, Elemento O, Rabbany SY, Rafii S (2012) Efficient direct reprogramming of mature amniotic cells into endothelial cells by ETS factors and TGFbeta suppression. Cell 151(3):559–575. doi: 10.1016/j.cell.2012.09.032 PubMedCentralPubMedGoogle Scholar
  77. 77.
    Morita R, Suzuki M, Kasahara H, Shimizu N, Shichita T, Sekiya T, Kimura A, Sasaki K, Yasukawa H, Yoshimura A (2015) ETS transcription factor ETV2 directly converts human fibroblasts into functional endothelial cells. Proc Natl Acad Sci USA 112(1):160–165. doi: 10.1073/pnas.1413234112 PubMedCentralPubMedGoogle Scholar
  78. 78.
    Schlaeger TM, Qin Y, Fujiwara Y, Magram J, Sato TN (1995) Vascular endothelial cell lineage-specific promoter in transgenic mice. Development 121:1089–1098PubMedGoogle Scholar
  79. 79.
    Aird WC, Jahroudi N, Weiler-Guettler H, Rayburn HB, Rosenberg RD (1995) Human von Willebrand factor gene sequences target expression to a subpopulation of endothelial cells in transgenic mice. Proc Natl Acad Sci USA 92(10):4567–4571PubMedCentralPubMedGoogle Scholar
  80. 80.
    Kappel A, Ronicke V, Damert A, Flamme I, Risau W, Breier G (1999) Identification of vascular endothelial growth factor (VEGF) receptor-2 (Flk-1) promoter/enhancer sequences sufficient for angioblast and endothelial cell-specific transcription in transgenic mice. Blood 93(12):4284–4292PubMedGoogle Scholar
  81. 81.
    Gory S, Vernet M, Laurent M, Dejana E, Dalmon J, Huber P (1999) The vascular endothelial-cadherin promoter directs endothelial-specific expression in transgenic mice. Blood 93(1):184–192PubMedGoogle Scholar
  82. 82.
    Iljin K, Petrova TV, Veikkola T, Kumar V, Poutanen M, Alitalo K (2002) A fluorescent Tie1 reporter allows monitoring of vascular development and endothelial cell isolation from transgenic mouse embryos. FASEB J 16(13):1764–1774. doi: 10.1096/fj.01-1043com PubMedGoogle Scholar
  83. 83.
    Seki T, Hong KH, Yun J, Kim SJ, Oh SP (2004) Isolation of a regulatory region of activin receptor-like kinase 1 gene sufficient for arterial endothelium-specific expression. Circ Res 94(8):e72–e77. doi: 10.1161/01.RES.0000127048.81744.31 PubMedGoogle Scholar
  84. 84.
    Mollica LR, Crawley JT, Liu K, Rance JB, Cockerill PN, Follows GA, Landry JR, Wells DJ, Lane DA (2006) Role of a 5’-enhancer in the transcriptional regulation of the human endothelial cell protein C receptor gene. Blood 108(4):1251–1259. doi: 10.1182/blood-2006-02-001461 PubMedGoogle Scholar
  85. 85.
    Okada Y, Yano K, Jin E, Funahashi N, Kitayama M, ADoi T, Spokes K, Beeler DL, Shih SC, Okada H, Danilov TA, Maynard E, Minami T, Oettgen P, Aird WC (2007) A three-kilobase fragment of the human Robo4 promoter directs cell type-specific expression in endothelium. Circ Res 100(12):1712–1722. doi: 10.1161/01.RES.0000269779.10644.dc PubMedGoogle Scholar
  86. 86.
    Jin E, Liu J, Suehiro J, Yuan L, Okada Y, Nikolova-Krstevski V, Yano K, Janes L, Beeler D, Spokes KC, Li D, Regan E, Shih SC, Oettgen P, Minami T, Aird WC (2009) Differential roles for ETS, CREB, and EGR binding sites in mediating VEGF receptor 1 expression in vivo. Blood 114(27):5557–5566. doi: 10.1182/blood-2009-05-220434 PubMedCentralPubMedGoogle Scholar
  87. 87.
    Wythe JD, Dang LT, Devine WP, Boudreau E, Artap ST, He D, Schachterle W, Stainier DY, Oettgen P, Black BL, Bruneau BG, Fish JE (2013) ETS factors regulate Vegf-dependent arterial specification. Dev Cell 26(1):45–58. doi: 10.1016/j.devcel.2013.06.007 PubMedCentralPubMedGoogle Scholar
  88. 88.
    Wang Y, Nakayama M, Pitulescu ME, Schmidt TS, Bochenek ML, Sakakibara A, Adams S, Davy A, Deutsch U, Luthi U, Barberis A, Benjamin LE, Makinen T, Nobes CD, Adams RH (2010) Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature 465(7297):483–486. doi: 10.1038/nature09002 PubMedGoogle Scholar
  89. 89.
    Shu XZ, Zhang LN, Zhang R, Zhang CJ, He HP, Zhou H, Wang N, Zhang TC (2015) Histone acetyltransferase p300 promotes MRTF-A-mediates transactivation of VE-cadherin gene in human umbilical vein endothelial cells. Gene 563(1):17–23. doi: 10.1016/j.gene.2015.02.076 PubMedGoogle Scholar
  90. 90.
    Holtz ML, Misra RP (2008) Endothelial-specific ablation of serum response factor causes hemorrhaging, yolk sac vascular failure, and embryonic lethality. BMC Dev Biol 8:65PubMedCentralPubMedGoogle Scholar
  91. 91.
    Meadows SM, Myers CT, Krieg PA (2011) Regulation of endothelial cell development by ETS transcription factors. Semin Cell Dev Biol 22(9):976–984. doi: 10.1016/j.semcdb.2011.09.009 PubMedCentralPubMedGoogle Scholar
  92. 92.
    De Val S, Chi NC, Meadows SM, Minovitsky S, Anderson JP, Harris IS, Ehlers ML, Agarwal P, Visel A, Xu SM, Pennacchio LA, Dubchak I, Krieg PA, Stainier DY, Black BL (2008) Combinatorial regulation of endothelial gene expression by ets and forkhead transcription factors. Cell 135(6):1053–1064PubMedCentralPubMedGoogle Scholar
  93. 93.
    Robinson AS, Materna SC, Barnes RM, De Val S, Xu SM, Black BL (2014) An arterial-specific enhancer of the human endothelin converting enzyme1 (ECE1) gene is synergistically activated by Sox17, FoxC2, and Etv2. Dev Biol 395(2):379–389. doi: 10.1016/j.ydbio.2014.08.027 PubMedGoogle Scholar
  94. 94.
    Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415PubMedGoogle Scholar
  95. 95.
    Topper JN, Cai J, Falb D, Gimbrone MA Jr (1996) Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc Natl Acad Sci USA 93(19):10417–10422PubMedCentralPubMedGoogle Scholar
  96. 96.
    Dekker RJ, van Soest S, Fontijn RD, Salamanca S, de Groot PG, VanBavel E, Pannekoek H, Horrevoets AJ (2002) Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Kruppel-like factor (KLF2). Blood 100(5):1689–1698. doi: 10.1182/blood-2002-01-0046 PubMedGoogle Scholar
  97. 97.
    Huddleson JP, Ahmad N, Srinivasan S, Lingrel JB (2005) Induction of KLF2 by fluid shear stress requires a novel promoter element activated by a phosphatidylinositol 3-kinase-dependent chromatin-remodeling pathway. J Biol Chem 280(24):23371–23379. doi: 10.1074/jbc.M413839200 PubMedGoogle Scholar
  98. 98.
    Khachigian LM, Anderson KR, Halnon NJ, Gimbrone MA Jr, Resnick N, Collins T (1997) Egr-1 is activated in endothelial cells exposed to fluid shear stress and interacts with a novel shear-stress-response element in the PDGF A-chain promoter. Arterioscler Thromb Vasc Biol 17(10):2280–2286PubMedGoogle Scholar
  99. 99.
    Zhang R, Min W, Sessa WC (1995) Functional analysis of the human endothelial nitric oxide synthase promoter. Sp1 and GATA factors are necessary for basal transcription in endothelial cells. J Biol Chem 270(25):15320–15326PubMedGoogle Scholar
  100. 100.
    SenBanerjee S, Lin Z, Atkins GB, Greif DM, Rao RM, Kumar A, Feinberg MW, Chen Z, Simon DI, Luscinskas FW, Michel TM, Gimbrone MA Jr, Garcia-Cardena G, Jain MK (2004) KLF2 Is a novel transcriptional regulator of endothelial proinflammatory activation. J Exp Med 199(10):1305–1315. doi: 10.1084/jem.20031132 PubMedCentralPubMedGoogle Scholar
  101. 101.
    Cordes KR, Srivastava D (2009) MicroRNA regulation of cardiovascular development. Circ Res 104:724–732PubMedCentralPubMedGoogle Scholar
  102. 102.
    Fan P, Chen Z, Tian P, Liu W, Jiao Y, Xue Y, Bhattacharya A, Wu J, Lu M, Guo Y, Cui Y, Gu W, Gu W, Yue J (2013) miRNA biogenesis enzyme Drosha is required for vascular smooth muscle cell survival. PLoS One 8(4):e60888. doi: 10.1371/journal.pone.0060888 PubMedCentralPubMedGoogle Scholar
  103. 103.
    Chen Z, Wu J, Yang C, Fan P, Balazs L, Jiao Y, Lu M, Gu W, Li C, Pfeffer LM, Tigyi G, Yue J (2012) DiGeorge syndrome critical region 8 (DGCR8) protein-mediated microRNA biogenesis is essential for vascular smooth muscle cell development in mice. J Biol Chem 287(23):19018–19028. doi: 10.1074/jbc.M112.351791 PubMedGoogle Scholar
  104. 104.
    Albinsson S, Suarez Y, Skoura A, Offermanns S, Miano JM, Sessa WC (2010) MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function. Arterioscler Thromb Vasc Biol 30:1118–1126PubMedCentralPubMedGoogle Scholar
  105. 105.
    Suarez Y, Fernandez-Hernando C, Yu J, Gerber SA, Harrison KD, Pober JS, Iruela-Arispe ML, Merkenschlager M, Sessa WC (2008) Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis. Proc Natl Acad Sci USA 105(37):14082–14087PubMedCentralPubMedGoogle Scholar
  106. 106.
    Kuehbacher A, Urbich C, Zeiher AM, Dimmeler S (2007) Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circ Res 101(1):59–68. doi: 10.1161/CIRCRESAHA.107.153916 PubMedGoogle Scholar
  107. 107.
    Gu S, Jin L, Zhang F, Sarnow P, Kay MA (2009) Biological basis for restriction of microRNA targets to the 3′ untranslated region in mammalian mRNAs. Nat Struct Mol Biol 16(2):144–150. doi: 10.1038/nsmb.1552 PubMedCentralPubMedGoogle Scholar
  108. 108.
    Ji R, Cheng Y, Yue J, Yang J, Liu X, Chen H, Dean DB, Zhang C (2007) MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res 100(11):1579–1588PubMedGoogle Scholar
  109. 109.
    Davis BN, Hilyard AC, Lagna G, Hata A (2008) SMAD proteins control DROSHA-mediated microRNA maturation. Nature 454:56–61PubMedCentralPubMedGoogle Scholar
  110. 110.
    Davis BN, Hilyard AC, Nguyen PH, Lagna G, Hata A (2009) Induction of microRNA-221 by platelet-derived growth factor signaling is critical for modulation of vascular smooth muscle phenotype. J Biol Chem 284(6):3728–3738PubMedCentralPubMedGoogle Scholar
  111. 111.
    Liu X, Cheng Y, Zhang S, Lin Y, Yang J, Zhang C (2009) A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia. Circ Res 104(4):476–487PubMedCentralPubMedGoogle Scholar
  112. 112.
    Sun SG, Zheng B, Han M, Fang XM, Li HX, Miao SB, Su M, Han Y, Shi HJ, Wen JK (2011) miR-146a and Kruppel-like factor 4 form a feedback loop to participate in vascular smooth muscle cell proliferation. EMBO Rep 12(1):56–62PubMedCentralPubMedGoogle Scholar
  113. 113.
    Wu WH, Hu CP, Chen XP, Zhang WF, Li XW, Xiong XM, Li YJ (2011) MicroRNA-130a mediates proliferation of vascular smooth muscle cells in hypertension. Am J Hypertens 24(10):1087–1093. doi: 10.1038/ajh.2011.116 PubMedGoogle Scholar
  114. 114.
    Reddy MA, Jin W, Villeneuve L, Wang M, Lanting L, Todorov I, Kato M, Natarajan R (2012) Pro-inflammatory role of microrna-200 in vascular smooth muscle cells from diabetic mice. Arterioscler Thromb Vasc Biol 32(3):721–729. doi: 10.1161/ATVBAHA.111.241109 PubMedCentralPubMedGoogle Scholar
  115. 115.
    Maegdefessel L, Spin JM, Raaz U, Eken SM, Toh R, Azuma J, Adam M, Nagakami F, Heymann HM, Chernugobova E, Jin H, Roy J, Hultgren R, Caidahl K, Schrepfer S, Hamsten A, Eriksson P, McConnell MV, Dalman RL, Tsao PS (2014) miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development. Nat Commun 5:5214. doi: 10.1038/ncomms6214 PubMedCentralPubMedGoogle Scholar
  116. 116.
    Balderman JA, Lee HY, Mahoney CE, Handy DE, White K, Annis S, Lebeche D, Hajjar RJ, Loscalzo J, Leopold JA (2012) Bone morphogenetic protein-2 decreases microRNA-30b and microRNA-30c to promote vascular smooth muscle cell calcification. J Am Heart Assoc 1(6):e003905. doi: 10.1161/JAHA.112.003905 PubMedCentralPubMedGoogle Scholar
  117. 117.
    Creemers EE, Tijsen AJ, Pinto YM (2012) Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease? Circ Res 110(3):483–495PubMedGoogle Scholar
  118. 118.
    Chen J, Yin H, Jiang Y, Radhakrishnan SK, Huang ZP, Li J, Shi Z, Kilsdonk EP, Gui Y, Wang DZ, Zheng XL (2011) Induction of microRNA-1 by myocardin in smooth muscle cells inhibits cell proliferation. Arterioscler Thromb Vasc Biol 31(2):368–375. doi: 10.1161/ATVBAHA.110.218149 PubMedCentralPubMedGoogle Scholar
  119. 119.
    Xie C, Huang H, Sun X, Guo Y, Hamblin M, Ritchie RP, Garcia-Barrio MT, Zhang J, Chen YE (2011) MicroRNA-1 regulates smooth muscle cell differentiation by repressing Kruppel-like factor 4. Stem Cells Dev 20(2):205–210PubMedCentralPubMedGoogle Scholar
  120. 120.
    Heidersbach A, Saxby C, Carver-Moore K, Huang Y, Ang YS, de Jong PJ, Ivey KN, Srivastava D (2013) microRNA-1 regulates sarcomere formation and suppresses smooth muscle gene expression in the mammalian heart. eLife 2:e01323. doi: 10.7554/eLife.01323 PubMedCentralPubMedGoogle Scholar
  121. 121.
    Wystub K, Besser J, Bachmann A, Boettger T, Braun T (2013) miR-1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development. PLoS Genet 9(9):e1003793. doi: 10.1371/journal.pgen.1003793 PubMedCentralPubMedGoogle Scholar
  122. 122.
    Zhao Y, Samal E, Srivastava D (2005) Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436:214–220PubMedGoogle Scholar
  123. 123.
    Liu N, Bezprozvannaya S, Williams AH, Qi X, Richardson JA, Bassel-Duby R, Olson EN (2008) microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Genes Dev 22(23):3242–3254PubMedCentralPubMedGoogle Scholar
  124. 124.
    Torella D, Iaconetti C, Catalucci D, Ellison GM, Leone A, Waring CD, Bochicchio A, Vicinanza C, Aquila I, Curcio A, Condorelli G, Indolfi C (2011) MicroRNA-133 controls vascular smooth muscle cell phenotypic switch in vitro and vascular remodeling in vivo. Circ Res 109:880–893PubMedGoogle Scholar
  125. 125.
    Madsen CS, Regan CP, Owens GK (1997) Interaction of CArG elements and a GC-rich repressor element in transcriptional regulation of the smooth muscle myosin heavy chain gene in vascular smooth muscle cells. J Biol Chem 272(47):29842–29851PubMedGoogle Scholar
  126. 126.
    Talasila A, Yu H, Ackers-Johnson M, Bot M, van Berkel T, Bennett MR, Bot I, Sinha S (2013) Myocardin regulates vascular response to injury through miR-24/-29a and platelet-derived growth factor receptor-beta. Arterioscler Thromb Vasc Biol 33(10):2355–2365. doi: 10.1161/ATVBAHA.112.301000 PubMedGoogle Scholar
  127. 127.
    Ackers-Johnson M, Talasila A, Sage AP, Long X, Bot I, Morrell NW, Bennett MR, Miano JM, Sinha S (2015) Myocardin regulates vascular smooth muscle cell inflammatory activation and disease. Arterioscler Thromb Vasc Biol 35(4):817–828. doi: 10.1161/ATVBAHA.114.305218 PubMedGoogle Scholar
  128. 128.
    Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee TH, Miano JM, Ivey KN, Srivastava D (2009) miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 460(7256):705–710PubMedCentralPubMedGoogle Scholar
  129. 129.
    Xin M, Small EM, Sutherland LB, Qi X, McAnally J, Plato CF, Richardson JA, Bassel-Duby R, Olson EN (2009) MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. Genes Dev 23(18):2166–2178PubMedCentralPubMedGoogle Scholar
  130. 130.
    Long X, Miano JM (2011) Transforming growth factor-β1 (TGF-β1) utilizes distinct pathways for the transcriptional activation of microRNA 143/145 in human coronary artery smooth muscle cells. J Biol Chem 286(34):30119–30129PubMedCentralPubMedGoogle Scholar
  131. 131.
    Boettger T, Beetz N, Kostin S, Schneider J, Kruger M, Hein L, Braun T (2009) Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster. J Clin Invest 119:2634–2647PubMedCentralPubMedGoogle Scholar
  132. 132.
    Cheng Y, Liu X, Yang J, Lin Y, Xu DZ, Lu Q, Deitch EA, Huo Y, Delphin ES, Zhang C (2009) MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ Res 105(2):158–166PubMedCentralPubMedGoogle Scholar
  133. 133.
    Turczynska KM, Sadegh MK, Hellstrand P, Sward K, Albinsson S (2012) MicroRNAs are essential for stretch-induced vascular smooth muscle contractile differentiation via microRNA (miR)-145-dependent expression of L-type calcium channels. J Biol Chem 287(23):19199–19206. doi: 10.1074/jbc.M112.341073 PubMedCentralPubMedGoogle Scholar
  134. 134.
    Caruso P, Dempsie Y, Stevens HC, McDonald RA, Long L, Lu R, White K, Mair KM, McClure JD, Southwood M, Upton P, Xin M, van Rooij E, Olson EN, Morrell NW, MacLean MR, Baker AH (2012) A role for miR-145 in pulmonary arterial hypertension: evidence from mouse models and patient samples. Circ Res 111(3):290–300. doi: 10.1161/CIRCRESAHA.112.267591 PubMedGoogle Scholar
  135. 135.
    Yu X, Zhang L, Wen G, Zhao H, Luong LA, Chen Q, Huang Y, Zhu J, Ye S, Xu Q, Wang W, Xiao Q (2014) Upregulated sirtuin 1 by miRNA-34a is required for smooth muscle cell differentiation from pluripotent stem cells. Cell Death Differ. doi: 10.1038/cdd.2014.206 Google Scholar
  136. 136.
    Londin E, Loher P, Telonis AG, Quann K, Clark P, Jing Y, Hatzimichael E, Kirino Y, Honda S, Lally M, Ramratnam B, Comstock CE, Knudsen KE, Gomella L, Spaeth GL, Hark L, Katz LJ, Witkiewicz A, Rostami A, Jimenez SA, Hollingsworth MA, Yeh JJ, Shaw CA, McKenzie SE, Bray P, Nelson PT, Zupo S, Van Roosbroeck K, Keating MJ, Calin GA, Yeo C, Jimbo M, Cozzitorto J, Brody JR, Delgrosso K, Mattick JS, Fortina P, Rigoutsos I (2015) Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs. Proc Natl Acad Sci USA 112(10):E1106–E1115. doi: 10.1073/pnas.1420955112 PubMedCentralPubMedGoogle Scholar
  137. 137.
    Elia L, Quintavalle M, Zhang J, Contu R, Cossu L, Latronico MV, Peterson KL, Indolfi C, Catalucci D, Chen J, Courtneidge SA, Condorelli G (2009) The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease. Cell Death Differ 16:1590–1598PubMedCentralPubMedGoogle Scholar
  138. 138.
    Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta N, Steer BM, Ingram AJ, Gupta M, Al Omran M, Teoh H, Marsden PA, Verma S (2012) MicroRNA-145 targeted therapy reduces atherosclerosis. Circulation 126(11 Suppl 1):S81–S90PubMedGoogle Scholar
  139. 139.
    Huang H, Xie C, Sun X, Ritchie RP, Zhang J, Chen YE (2010) miR-10a contributes to retinoid acid-induced smooth muscle cell differentiation. J Biol Chem 285(13):9383–9389PubMedCentralPubMedGoogle Scholar
  140. 140.
    Jiang Y, Yin H, Zheng XL (2010) MicroRNA-1 inhibits myocardin-induced contractility of human vascular smooth muscle cells. J Cell Physiol 225(2):506–511PubMedGoogle Scholar
  141. 141.
    Leeper NJ, Raiesdana A, Kojima Y, Chun HJ, Azuma J, Maegdefessel L, Kundu RK, Quertermous T, Tsao PS, Spin JM (2011) MicroRNA-26a is a novel regulator of vascular smooth muscle cell function. J Cell Physiol 226(4):1035–1043PubMedCentralPubMedGoogle Scholar
  142. 142.
    Poliseno L, Tuccoli A, Mariani L, Evangelista M, Citti L, Woods K, Mercatanti A, Hammond S, Rainaldi G (2006) MicroRNAs modulate the angiogenic properties of HUVECs. Blood 108(9):3068–3071. doi: 10.1182/blood-2006-01-012369 PubMedGoogle Scholar
  143. 143.
    Kumar S, Kim CW, Simmons RD, Jo H (2014) Role of flow-sensitive microRNAs in endothelial dysfunction and atherosclerosis: mechanosensitive athero-miRs. Arterioscler Thromb Vasc Biol 34(10):2206–2216. doi: 10.1161/ATVBAHA.114.303425 PubMedGoogle Scholar
  144. 144.
    Neth P, Nazari-Jahantigh M, Schober A, Weber C (2013) MicroRNAs in flow-dependent vascular remodelling. Cardiovasc Res 99(2):294–303. doi: 10.1093/cvr/cvt096 PubMedGoogle Scholar
  145. 145.
    Chen K, Fan W, Wang X, Ke X, Wu G, Hu C (2012) MicroRNA-101 mediates the suppressive effect of laminar shear stress on mTOR expression in vascular endothelial cells. Biochem Biophys Res Commun 427(1):138–142. doi: 10.1016/j.bbrc.2012.09.026 PubMedGoogle Scholar
  146. 146.
    Qin X, Wang X, Wang Y, Tang Z, Cui Q, Xi J, Li YS, Chien S, Wang N (2010) MicroRNA-19a mediates the suppressive effect of laminar flow on cyclin D1 expression in human umbilical vein endothelial cells. Proc Natl Acad Sci USA 107(7):3240–3244. doi: 10.1073/pnas.0914882107 PubMedCentralPubMedGoogle Scholar
  147. 147.
    Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets AJ, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M, Braun T, Urbich C, Boon RA, Dimmeler S (2012) Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol 14(3):249–256. doi: 10.1038/ncb2441 PubMedGoogle Scholar
  148. 148.
    Kohlstedt K, Trouvain C, Boettger T, Shi L, Fisslthaler B, Fleming I (2013) AMP-activated protein kinase regulates endothelial cell angiotensin-converting enzyme expression via p53 and the post-transcriptional regulation of microRNA-143/145. Circ Res 112(8):1150–1158. doi: 10.1161/CIRCRESAHA.113.301282 PubMedGoogle Scholar
  149. 149.
    Climent-Salarich M, Quintavalle M, Miragoli M, Chen J, Condorelli G, Elia L (2015) TGFbeta triggers miR-143/145 transfer from smooth muscle cells to endothelial cells, thereby modulating vessel stabilization. Circ Res. doi: 10.1161/CIRCRESAHA.116.305178 Google Scholar
  150. 150.
    Fang Y, Shi C, Manduchi E, Civelek M, Davies PF (2010) MicroRNA-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitro. Proc Natl Acad Sci USA 107(30):13450–13455. doi: 10.1073/pnas.1002120107 PubMedCentralPubMedGoogle Scholar
  151. 151.
    Njock MS, Cheng HS, Dang LT, Nazari-Jahantigh M, Lau AC, Boudreau E, Roufaiel M, Cybulsky MI, Schober A, Fish JE (2015) Endothelial cells suppress monocyte activation through secretion of extracellular vesicles containing anti-inflammatory microRNAs. Blood. doi: 10.1182/blood-2014-11-611046 PubMedCentralPubMedGoogle Scholar
  152. 152.
    Ni CW, Qiu H, Jo H (2011) MicroRNA-663 upregulated by oscillatory shear stress plays a role in inflammatory response of endothelial cells. Am J Physiol Heart Circ Physiol 300(5):H1762–H1769. doi: 10.1152/ajpheart.00829.2010 PubMedCentralPubMedGoogle Scholar
  153. 153.
    Wu W, Xiao H, Laguna-Fernandez A, Villarreal G Jr, Wang KC, Geary GG, Zhang Y, Wang WC, Huang HD, Zhou J, Li YS, Chien S, Garcia-Cardena G, Shyy JY (2011) Flow-dependent regulation of Kruppel-like factor 2 is mediated by microRNA-92a. Circulation 124(5):633–641. doi: 10.1161/CIRCULATIONAHA.110.005108 PubMedGoogle Scholar
  154. 154.
    Fan W, Fang R, Wu X, Liu J, Feng M, Dai G, Chen G, Wu G (2015) Shear-sensitive microRNA-34a modulates flow-dependent regulation of endothelial inflammation. J Cell Sci 128(1):70–80. doi: 10.1242/jcs.154252 PubMedGoogle Scholar
  155. 155.
    Harris TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ (2008) MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci USA 105(5):1516–1521. doi: 10.1073/pnas.0707493105 PubMedCentralPubMedGoogle Scholar
  156. 156.
    Wang S, Aurora AB, Johnson BA, Qi X, McNally J, Hill JA, Richardson JA, Bassel-Duby R, Olson EN (2008) The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell 15:261–271PubMedCentralPubMedGoogle Scholar
  157. 157.
    Harris TA, Yamakuchi M, Kondo M, Oettgen P, Lowenstein CJ (2010) Ets-1 and Ets-2 regulate the expression of microRNA-126 in endothelial cells. Arterioscler Thromb Vasc Biol 30(10):1990–1997. doi: 10.1161/ATVBAHA.110.211706 PubMedCentralPubMedGoogle Scholar
  158. 158.
    Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, Ivey KN, Bruneau BG, Stainier DY, Srivastava D (2008) miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell 15(2):272–284PubMedCentralPubMedGoogle Scholar
  159. 159.
    Schmidt M, Paes K, De Maziere A, Smyczek T, Yang S, Gray A, French D, Kasman I, Klumperman J, Rice DS, Ye W (2007) EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution. Development 134(16):2913–2923. doi: 10.1242/dev.002576 PubMedGoogle Scholar
  160. 160.
    Kuhnert F, Mancuso MR, Hampton J, Stankunas K, Asano T, Chen CZ, Kuo CJ (2008) Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126. Development 135(24):3989–3993. doi: 10.1242/dev.029736 PubMedGoogle Scholar
  161. 161.
    Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, Burchfield J, Fox H, Doebele C, Ohtani K, Chavakis E, Potente M, Tjwa M, Urbich C, Zeiher AM, Dimmeler S (2009) MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 324(5935):1710–1713. doi: 10.1126/science.1174381 PubMedGoogle Scholar
  162. 162.
    Zhao T, Li J, Chen AF (2010) MicroRNA-34a induces endothelial progenitor cell senescence and impedes its angiogenesis via suppressing silent information regulator 1. Am J Physiol Endocrinol Metab 299(1):E110–E116. doi: 10.1152/ajpendo.00192.2010 PubMedCentralPubMedGoogle Scholar
  163. 163.
    Ghosh G, Subramanian IV, Adhikari N, Zhang X, Joshi HP, Basi D, Chandrashekhar YS, Hall JL, Roy S, Zeng Y, Ramakrishnan S (2010) Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-alpha isoforms and promotes angiogenesis. J Clin Invest 120(11):4141–4154. doi: 10.1172/JCI42980 PubMedCentralPubMedGoogle Scholar
  164. 164.
    Cunningham A, Dokun AO (2014) MicroRNAs as potential therapeutic targets in peripheral artery disease. Int J Diabetol Vasc Dis Res 2(6):67–70Google Scholar
  165. 165.
    Shi L, Fisslthaler B, Zippel N, Fromel T, Hu J, Elgheznawy A, Heide H, Popp R, Fleming I (2013) MicroRNA-223 antagonizes angiogenesis by targeting beta1 integrin and preventing growth factor signaling in endothelial cells. Circ Res 113(12):1320–1330. doi: 10.1161/CIRCRESAHA.113.301824 PubMedGoogle Scholar
  166. 166.
    Kane NM, Howard L, Descamps B, Meloni M, McClure J, Lu R, McCahill A, Breen C, Mackenzie RM, Delles C, Mountford JC, Milligan G, Emanueli C, Baker AH (2012) Role of microRNAs 99b, 181a, and 181b in the differentiation of human embryonic stem cells to vascular endothelial cells. Stem Cells 30(4):643–654. doi: 10.1002/stem.1026 PubMedCentralPubMedGoogle Scholar
  167. 167.
    Di Bernardini E, Campagnolo P, Margariti A, Zampetaki A, Karamariti E, Hu Y, Xu Q (2014) Endothelial lineage differentiation from induced pluripotent stem cells is regulated by microRNA-21 and transforming growth factor beta2 (TGF-beta2) pathways. J Biol Chem 289(6):3383–3393. doi: 10.1074/jbc.M113.495531 PubMedCentralPubMedGoogle Scholar
  168. 168.
    Miller CL, Haas U, Diaz R, Leeper NJ, Kundu RK, Patlolla B, Assimes TL, Kaiser FJ, Perisic L, Hedin U, Maegdefessel L, Schunkert H, Erdmann J, Quertermous T, Sczakiel G (2014) Coronary heart disease-associated variation in TCF21 disrupts a miR-224 binding site and miRNA-mediated regulation. PLoS Genet 10(3):e1004263. doi: 10.1371/journal.pgen.1004263 PubMedCentralPubMedGoogle Scholar
  169. 169.
    Kapranov P, Cawley SE, Drenkow J, Bekiranov S, Strausberg RL, Fodor SPA, Gingeras TR (2002) Large-scale transcriptional activity in chromosomes 21 and 22. Science 296:916–919PubMedGoogle Scholar
  170. 170.
    Mercer TR, Gerhardt DJ, Dinger ME, Crawford J, Trapnell C, Jeddeloh JA, Mattick JS, Rinn JL (2012) Targeted RNA sequencing reveals the deep complexity of the human transcriptome. Nat Biotechnol 30(1):99–104Google Scholar
  171. 171.
    Hangauer MJ, Vaughn IW, McManus MT (2013) Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs. PLoS Genet 9(6):e1003569. doi: 10.1371/journal.pgen.1003569 PubMedCentralPubMedGoogle Scholar
  172. 172.
    Volders PJ, Verheggen K, Menschaert G, Vandepoele K, Martens L, Vandesompele J, Mestdagh P (2015) An update on LNCipedia: a database for annotated human lncRNA sequences. Nucleic Acids Res 43(Database issue):D174–D180. doi: 10.1093/nar/gku1060 PubMedCentralPubMedGoogle Scholar
  173. 173.
    Rinn JL, Chang HY (2012) Genome regulation by long noncoding RNAs. Annu Rev Biochem 81:145–166PubMedGoogle Scholar
  174. 174.
    Yang F, Zhang H, Mei Y, Wu M (2014) Reciprocal regulation of HIF-1alpha and lincRNA-p21 modulates the Warburg effect. Mol Cell 53(1):88–100. doi: 10.1016/j.molcel.2013.11.004 PubMedGoogle Scholar
  175. 175.
    Ilott NE, Heward JA, Roux B, Tsitsiou E, Fenwick PS, Lenzi L, Goodhead I, Hertz-Fowler C, Heger A, Hall N, Donnelly LE, Sims D, Lindsay MA (2014) Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes. Nat Commun 5:3979. doi: 10.1038/ncomms4979 Google Scholar
  176. 176.
    Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, Lajoie BR, Protacio A, Flynn RA, Gupta RA, Wysocka J, Lei M, Dekker J, Helms JA, Chang HY (2011) A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472(7341):120–124. doi: 10.1038/nature09819 PubMedCentralPubMedGoogle Scholar
  177. 177.
    Sauvageau M, Goff LA, Lodato S, Bonev B, Groff AF, Gerhardinger C, Sanchez-Gomez DB, Hacisuleyman E, Li E, Spence M, Liapis SC, Mallard W, Morse M, Swerdel MR, D’Ecclessis MF, Moore JC, Lai V, Gong G, Yancopoulos GD, Frendewey D, Kellis M, Hart RP, Valenzuela DM, Arlotta P, Rinn JL (2013) Multiple knockout mouse models reveal lincRNAs are required for life and brain development. eLife 2:e01749. doi: 10.7554/eLife.01749 PubMedCentralPubMedGoogle Scholar
  178. 178.
    Wilusz JE, Sunwoo H, Spector DL (2009) Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 23(13):1494–1504. doi: 10.1101/gad.1800909 PubMedCentralPubMedGoogle Scholar
  179. 179.
    Bonasio R, Shiekhattar R (2014) Regulation of transcription by long noncoding RNAs. Annu Rev Genet 48:433–455. doi: 10.1146/annurev-genet-120213-092323 PubMedCentralPubMedGoogle Scholar
  180. 180.
    Ulitsky I, Bartel DP (2013) lincRNAs: genomics, evolution, and mechanisms. Cell 154(1):26–46. doi: 10.1016/j.cell.2013.06.020 PubMedCentralPubMedGoogle Scholar
  181. 181.
    Faghihi MA, Wahlestedt C (2009) Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol 10(9):637–643. doi: 10.1038/nrm2738 PubMedGoogle Scholar
  182. 182.
    Tahira AC, Kubrusly MS, Faria MF, Dazzani B, Fonseca RS, Maracaja-Coutinho V, Verjovski-Almeida S, Machado MC, Reis EM (2011) Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer. Mol Cancer 10:141. doi: 10.1186/1476-4598-10-141 PubMedCentralPubMedGoogle Scholar
  183. 183.
    Orom UA, Shiekhattar R (2013) Long noncoding RNAs usher in a new era in the biology of enhancers. Cell 154:1190–1193PubMedCentralPubMedGoogle Scholar
  184. 184.
    Karreth FA, Reschke M, Ruocco A, Ng C, Chapuy B, Leopold V, Sjoberg M, Keane TM, Verma A, Ala U, Tay Y, Wu D, Seitzer N, Velasco-Herrera MD, Bothmer A, Fung J, Langellotto F, Rodig SJ, Elemento O, Shipp MA, Adams DJ, Chiarle R, Pandolfi PP (2015) The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo. Cell 161(2):319–332. doi: 10.1016/j.cell.2015.02.043 PubMedGoogle Scholar
  185. 185.
    Lasda E, Parker R (2014) Circular RNAs: diversity of form and function. RNA 20(12):1829–1842. doi: 10.1261/rna.047126.114 PubMedGoogle Scholar
  186. 186.
    Halley P, Kadakkuzha BM, Faghihi MA, Magistri M, Zeier Z, Khorkova O, Coito C, Hsiao J, Lawrence M, Wahlestedt C (2014) Regulation of the apolipoprotein gene cluster by a long noncoding RNA. Cell Rep 6(1):222–230. doi: 10.1016/j.celrep.2013.12.015 PubMedCentralPubMedGoogle Scholar
  187. 187.
    Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, Tramontano A, Bozzoni I (2011) A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147(2):358–369PubMedCentralPubMedGoogle Scholar
  188. 188.
    Gong C, Maquat LE (2011) lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3’ UTRs via Alu elements. Nature 470(7333):284–288PubMedCentralPubMedGoogle Scholar
  189. 189.
    Carrieri C, Cimatti L, Biagioli M, Beugnet A, Zucchelli S, Fedele S, Pesce E, Ferrer I, Collavin L, Santoro C, Forrest AR, Carninci P, Biffo S, Stupka E, Gustincich S (2012) Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature 491(7424):454–457PubMedGoogle Scholar
  190. 190.
    Willingham AT, Orth AP, Batalov S, Peters EC, Wen BG, Aza-Blanc P, Hogenesch JB, Schultz PG (2005) A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science 309(5740):1570–1573. doi: 10.1126/science.1115901 PubMedGoogle Scholar
  191. 191.
    Wang P, Xue Y, Han Y, Lin L, Wu C, Xu S, Jiang Z, Xu J, Liu Q, Cao X (2014) The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science 344(6181):310–313. doi: 10.1126/science.1251456 PubMedGoogle Scholar
  192. 192.
    Liu B, Sun L, Liu Q, Gong C, Yao Y, Lv X, Lin L, Yao H, Su F, Li D, Zeng M, Song E (2015) A cytoplasmic NF-kappaB interacting long noncoding RNA blocks IkappaB phosphorylation and suppresses breast cancer metastasis. Cancer Cell 27(3):370–381. doi: 10.1016/j.ccell.2015.02.004 PubMedGoogle Scholar
  193. 193.
    Zhang B, Gunawardane L, Niazi F, Jahanbani F, Chen X, Valadkhan S (2014) A novel RNA motif mediates the strict nuclear localization of a long noncoding RNA. Mol Cell Biol 34(12):2318–2329. doi: 10.1128/MCB.01673-13 PubMedCentralPubMedGoogle Scholar
  194. 194.
    Guttman M, Russell P, Ingolia NT, Weissman JS, Lander ES (2013) Ribosome profiling provides evidence that large noncoding RNAs do not encode proteins. Cell 154(1):240–251. doi: 10.1016/j.cell.2013.06.009 PubMedCentralPubMedGoogle Scholar
  195. 195.
    Pauli A, Norris ML, Valen E, Chew GL, Gagnon JA, Zimmerman S, Mitchell A, Ma J, Dubrulle J, Reyon D, Tsai SQ, Joung JK, Saghatelian A, Schier AF (2014) Toddler: an embryonic signal that promotes cell movement via Apelin receptors. Science 343(6172):1248636. doi: 10.1126/science.1248636 PubMedCentralPubMedGoogle Scholar
  196. 196.
    Anderson DM, Anderson KM, Chang CL, Makarewich CA, Nelson BR, McAnally JR, Kasaragod P, Shelton JM, Liou J, Bassel-Duby R, Olson EN (2015) A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell 160(4):595–606. doi: 10.1016/j.cell.2015.01.009 PubMedGoogle Scholar
  197. 197.
    Han DKM, Liau G (1992) Identification and characterization of developmentally regulated genes in vascular smooth muscle cells. Circ Res 71(3):711–719PubMedGoogle Scholar
  198. 198.
    Han DK, Khaing ZZ, Pollock RA, Haudenschild CC, Liau G (1996) H19, a marker of developmental transition, is reexpressed in human atherosclerotic plaques and is regulated by the insulin family of growth factors in cultured rabbit smooth muscle cells. J Clin Invest 97(5):1276–1285. doi: 10.1172/JCI118543 PubMedCentralPubMedGoogle Scholar
  199. 199.
    Kim DK, Zhang L, Dzau VJ, Pratt RE (1994) H19, a developmentally regulated gene, is reexpressed in rat vascular smooth muscle cells after injury. J Clin Invest 93:355–360PubMedCentralPubMedGoogle Scholar
  200. 200.
    Kallen AN, Zhou XB, Xu J, Qiao C, Ma J, Yan L, Lu L, Liu C, Yi JS, Zhang H, Min W, Bennett AM, Gregory RI, Ding Y, Huang Y (2013) The imprinted H19 lncRNA antagonizes let-7 microRNAs. Mol Cell 52(1):101–112. doi: 10.1016/j.molcel.2013.08.027 PubMedGoogle Scholar
  201. 201.
    Ding Z, Wang X, Schnackenberg L, Khaidakov M, Liu S, Singla S, Dai Y, Mehta JL (2013) Regulation of autophagy and apoptosis in response to ox-LDL in vascular smooth muscle cells, and the modulatory effects of the microRNA hsa-let-7 g. Int J Cardiol 168(2):1378–1385. doi: 10.1016/j.ijcard.2012.12.045 PubMedGoogle Scholar
  202. 202.
    Onyango P, Feinberg AP (2011) A nucleolar protein, H19 opposite tumor suppressor (HOTS), is a tumor growth inhibitor encoded by a human imprinted H19 antisense transcript. Proc Natl Acad Sci USA 108(40):16759–16764. doi: 10.1073/pnas.1110904108 PubMedCentralPubMedGoogle Scholar
  203. 203.
    Pasmant E, Sabbagh A, Vidaud M, Bieche I (2011) ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J 25(2):444–448. doi: 10.1096/fj.10-172452 PubMedGoogle Scholar
  204. 204.
    Kotake Y, Nakagawa T, Kitagawa K, Suzuki S, Liu N, Kitagawa M, Xiong Y (2011) Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene. Oncogene 30(16):1956–1962. doi: 10.1038/onc.2010.568 PubMedCentralPubMedGoogle Scholar
  205. 205.
    Motterle A, Pu X, Wood H, Xiao Q, Gor S, Ng FL, Chan K, Cross F, Shohreh B, Poston RN, Tucker AT, Caulfield MJ, Ye S (2012) Functional analyses of coronary artery disease associated variation on chromosome 9p21 in vascular smooth muscle cells. Hum Mol Genet 21(18):4021–4029. doi: 10.1093/hmg/dds224 PubMedCentralPubMedGoogle Scholar
  206. 206.
    Visel A, Zhu Y, May D, Afzal V, Gong E, Attanasio C, Blow MJ, Cohen JC, Rubin EM, Pennacchio LA (2010) Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice. Nature 464(7287):409–412PubMedCentralPubMedGoogle Scholar
  207. 207.
    Robb GB, Carson AR, Tai SC, Fish JE, Singh S, Yamada T, Scherer SW, Nakabayashi K, Marsden PA (2004) Post-transcriptional regulation of endothelial nitric-oxide synthase by an overlapping antisense mRNA transcript. J Biol Chem 279(36):37982–37996. doi: 10.1074/jbc.M400271200 PubMedGoogle Scholar
  208. 208.
    Leung A, Trac C, Jin W, Lanting L, Akbany A, Saetrom P, Schones DE, Natarajan R (2013) Novel long noncoding RNAs are regulated by angiotensin II in vascular smooth muscle cells. Circ Res 113(3):266–278. doi: 10.1161/CIRCRESAHA.112.300849 PubMedCentralPubMedGoogle Scholar
  209. 209.
    Bell RD, Long X, Lin M, Bergmann JH, Nanda V, Cowan SL, Zhou Q, Han Y, Spector DL, Zheng D, Miano JM (2014) Identification and initial functional characterization of a human vascular cell-enriched long noncoding RNA. Arterioscler Thromb Vasc Biol 34(6):1249–1259. doi: 10.1161/ATVBAHA.114.303240 PubMedCentralPubMedGoogle Scholar
  210. 210.
    Li X, Jiang XY, Ge J, Wang J, Chen GJ, Xu L, Xie DY, Yuan TY, Zhang DS, Zhang H, Chen YH (2014) Aberrantly expressed lncRNAs in primary varicose great saphenous veins. PLoS One 9(1):e86156. doi: 10.1371/journal.pone.0086156 PubMedCentralPubMedGoogle Scholar
  211. 211.
    Li L, Li X, The E, Wang LJ, Yuan TY, Wang SY, Feng J, Wang J, Liu Y, Wu YH, Ma XE, Ge J, Cui YY, Jiang XY (2015) Low expression of lncRNA-GAS5 is implicated in human primary varicose great saphenous veins. PLoS One 10(3):e0120550. doi: 10.1371/journal.pone.0120550 PubMedGoogle Scholar
  212. 212.
    Vigetti D, Deleonibus S, Moretto P, Bowen T, Fischer JW, Grandoch M, Oberhuber A, Love DC, Hanover JA, Cinquetti R, Karousou E, Viola M, D’Angelo ML, Hascall VC, De Luca G, Passi A (2014) Natural antisense transcript for hyaluronan synthase 2 (HAS2-AS1) induces transcription of HAS2 via protein O-GlcNAcylation. J Biol Chem 289(42):28816–28826. doi: 10.1074/jbc.M114.597401 PubMedGoogle Scholar
  213. 213.
    Wu G, Cai J, Han Y, Chen J, Huang ZP, Chen C, Cai Y, Huang H, Yang Y, Liu Y, Xu Z, He D, Zhang X, Hu X, Pinello L, Zhong D, He F, Yuan GC, Wang DZ, Zeng C (2014) LincRNA-p21 regulates neointima formation, vascular smooth muscle cell proliferation, apoptosis, and atherosclerosis by enhancing p53 activity. Circulation 130(17):1452–1465. doi: 10.1161/CIRCULATIONAHA.114.011675 PubMedGoogle Scholar
  214. 214.
    Zhao Y, Feng G, Wang Y, Yue Y, Zhao W (2014) Regulation of apoptosis by long non-coding RNA HIF1A-AS1 in VSMCs: implications for TAA pathogenesis. Int J Clin Exp Pathol 7(11):7643–7652PubMedCentralPubMedGoogle Scholar
  215. 215.
    Fish JE, Matouk CC, Yeboah E, Bevan SC, Khan M, Patil K, Ohh M, Marsden PA (2007) Hypoxia-inducible expression of a natural cis-antisense transcript inhibits endothelial nitric-oxide synthase. J Biol Chem 282(21):15652–15666PubMedGoogle Scholar
  216. 216.
    Li K, Blum Y, Verma A, Liu Z, Pramanik K, Leigh NR, Chun CZ, Samant GV, Zhao B, Garnaas MK, Horswill MA, Stanhope SA, North PE, Miao RQ, Wilkinson GA, Affolter M, Ramchandran R (2010) A noncoding antisense RNA in tie-1 locus regulates tie-1 function in vivo. Blood 115(1):133–139PubMedCentralPubMedGoogle Scholar
  217. 217.
    Michalik KM, You X, Manavski Y, Doddaballapur A, Zornig M, Braun T, John D, Ponomareva Y, Chen W, Uchida S, Boon RA, Dimmeler S (2014) Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res 114(9):1389–1397. doi: 10.1161/CIRCRESAHA.114.303265 PubMedGoogle Scholar
  218. 218.
    Liu JY, Yao J, Li XM, Song YC, Wang XQ, Li YJ, Yan B, Jiang Q (2014) Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus. Cell Death Dis 5:e1506. doi: 10.1038/cddis.2014.466 PubMedGoogle Scholar
  219. 219.
    Puthanveetil P, Chen S, Feng B, Gautam A, Chakrabarti S (2015) Long non-coding RNA MALAT1 regulates hyperglycaemia induced inflammatory process in the endothelial cells. J Cell Mol Med. doi: 10.1111/jcmm.12576 PubMedCentralPubMedGoogle Scholar
  220. 220.
    Yan B, Yao J, Liu JY, Li XM, Wang XQ, Li YJ, Tao ZF, Song YC, Chen Q, Jiang Q (2015) lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA. Circ Res 116(7):1143–1156. doi: 10.1161/CIRCRESAHA.116.305510 PubMedGoogle Scholar
  221. 221.
    Ge D, Han L, Huang S, Peng N, Wang P, Jiang Z, Zhao J, Su L, Zhang S, Zhang Y, Kung H, Zhao B, Miao J (2014) Identification of a novel MTOR activator and discovery of a competing endogenous RNA regulating autophagy in vascular endothelial cells. Autophagy 10(6):957–971. doi: 10.4161/auto.28363 PubMedCentralPubMedGoogle Scholar
  222. 222.
    Li JH, Liu S, Zhou H, Qu LH, Yang JH (2014) starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res 42(Database issue):D92–D97. doi: 10.1093/nar/gkt1248 PubMedCentralPubMedGoogle Scholar
  223. 223.
    Kurian L, Aguirre A, Sancho-Martinez I, Benner C, Hishida T, Nguyen TB, Reddy P, Nivet E, Krause MN, Nelles DA, Esteban CR, Campistol JM, Yeo GW, Izpisua Belmonte JC (2015) Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development. Circulation 131(14):1278–1290. doi: 10.1161/CIRCULATIONAHA.114.013303 PubMedCentralPubMedGoogle Scholar
  224. 224.
    Li K, Chowdhury T, Vakeel P, Koceja C, Sampath V, Ramchandran R (2015) Delta-like4 mRNA is regulated by adjacent natural antisense transcripts. Vascular Cell 7(3)Google Scholar
  225. 225.
    Zhang Y, Yang L, Chen LL (2014) Life without A tail: new formats of long noncoding RNAs. Int J Biochem Cell Biol 54:338–349. doi: 10.1016/j.biocel.2013.10.009 PubMedGoogle Scholar
  226. 226.
    St Laurent G, Wahlestedt C, Kapranov P (2015) The landscape of long noncoding RNA classification. Trends Genet. doi: 10.1016/j.tig.2015.03.007 PubMedGoogle Scholar
  227. 227.
    Wright MW (2014) A short guide to long non-coding RNA gene nomenclature. Hum Genomics 8:7. doi: 10.1186/1479-7364-8-7 PubMedCentralPubMedGoogle Scholar
  228. 228.
    Raney BJ, Cline MS, Rosenbloom KR, Dreszer TR, Learned K, Barber GP, Meyer LR, Sloan CA, Malladi VS, Roskin KM, Suh BB, Hinrichs AS, Clawson H, Zweig AS, Kirkup V, Fujita PA, Rhead B, Smith KE, Pohl A, Kuhn RM, Karolchik D, Haussler D, Kent WJ (2011) ENCODE whole-genome data in the UCSC genome browser (2011 update). Nucleic Acids Res 39(Database issue):D871–D875PubMedCentralPubMedGoogle Scholar
  229. 229.
    Zhang M, Ren Y, Wang Y, Wang R, Zhou Q, Peng Y, Li Q, Yu M, Jiang Y (2015) Regulation of smooth muscle contractility by competing endogenous mRNAs in intracranial aneurysms. J Neuropathol Exp Neurol 74(5):411–424. doi: 10.1097/NEN.0000000000000185 PubMedGoogle Scholar
  230. 230.
    Ning S, Zhao Z, Ye J, Wang P, Zhi H, Li R, Wang T, Li X (2014) LincSNP: a database of linking disease-associated SNPs to human large intergenic non-coding RNAs. BMC Bioinform 15:152. doi: 10.1186/1471-2105-15-152 Google Scholar
  231. 231.
    Gong J, Liu W, Zhang J, Miao X, Guo AY (2015) lncRNASNP: a database of SNPs in lncRNAs and their potential functions in human and mouse. Nucleic Acids Res 43(Database issue):D181–D186. doi: 10.1093/nar/gku1000 PubMedGoogle Scholar
  232. 232.
    Bassett AR, Akhtar A, Barlow DP, Bird AP, Brockdorff N, Duboule D, Ephrussi A, Ferguson-Smith AC, Gingeras TR, Haerty W, Higgs DR, Miska EA, Ponting CP (2014) Considerations when investigating lncRNA function in vivo. eLife 3:e03058. doi: 10.7554/eLife.03058 PubMedCentralPubMedGoogle Scholar
  233. 233.
    Chu C, Spitale RC, Chang HY (2015) Technologies to probe functions and mechanisms of long noncoding RNAs. Nat Struct Mol Biol 22(1):29–35. doi: 10.1038/nsmb.2921 PubMedGoogle Scholar
  234. 234.
    Chen R, Mias GI, Li-Pook-Than J, Jiang L, Lam HY, Chen R, Miriami E, Karczewski KJ, Hariharan M, Dewey FE, Cheng Y, Clark MJ, Im H, Habegger L, Balasubramanian S, O’Huallachain M, Dudley JT, Hillenmeyer S, Haraksingh R, Sharon D, Euskirchen G, Lacroute P, Bettinger K, Boyle AP, Kasowski M, Grubert F, Seki S, Garcia M, Whirl-Carrillo M, Gallardo M, Blasco MA, Greenberg PL, Snyder P, Klein TE, Altman RB, Butte AJ, Ashley EA, Gerstein M, Nadeau KC, Tang H, Snyder M (2012) Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell 148(6):1293–1307. doi: 10.1016/j.cell.2012.02.009 PubMedCentralPubMedGoogle Scholar
  235. 235.
    Kang K, Peng X, Zhang X, Wang Y, Zhang L, Gao L, Weng T, Zhang H, Ramchandran R, Raj JU, Gou D, Liu L (2013) MicroRNA-124 suppresses the transactivation of nuclear factor of activated T cells by targeting multiple genes and inhibits the proliferation of pulmonary artery smooth muscle cells. J Biol Chem 288(35):25414–25427. doi: 10.1074/jbc.M113.460287 PubMedCentralPubMedGoogle Scholar
  236. 236.
    Villeneuve LM, Kato M, Reddy MA, Wang M, Lanting L, Natarajan R (2010) Enhanced levels of microRNA-125b in vascular smooth muscle cells of diabetic db/db mice lead to increased inflammatory gene expression by targeting the histone methyltransferase Suv39h1. Diabetes 59(11):2904–2915. doi: 10.2337/db10-0208 PubMedCentralPubMedGoogle Scholar
  237. 237.
    Choe N, Kwon JS, Kim JR, Eom GH, Kim Y, Nam KI, Ahn Y, Kee HJ, Kook H (2013) The microRNA miR-132 targets Lrrfip1 to block vascular smooth muscle cell proliferation and neointimal hyperplasia. Atherosclerosis 229(2):348–355. doi: 10.1016/j.atherosclerosis.2013.05.009 PubMedGoogle Scholar
  238. 238.
    Li S, Ran Y, Zhang D, Chen J, Li S, Zhu D (2013) MicroRNA-138 plays a role in hypoxic pulmonary vascular remodelling by targeting Mst1. Biochem J 452(2):281–291. doi: 10.1042/BJ20120680 PubMedGoogle Scholar
  239. 239.
    Wang YS, Wang HY, Liao YC, Tsai PC, Chen KC, Cheng HY, Lin RT, Juo SH (2012) MicroRNA-195 regulates vascular smooth muscle cell phenotype and prevents neointimal formation. Cardiovasc Res 95(4):517–526. doi: 10.1093/cvr/cvs223 PubMedGoogle Scholar
  240. 240.
    Courboulin A, Paulin R, Giguere NJ, Saksouk N, Perreault T, Meloche J, Paquet ER, Biardel S, Provencher S, Cote J, Simard MJ, Bonnet S (2011) Role for miR-204 in human pulmonary arterial hypertension. J Exp Med 208(3):535–548. doi: 10.1084/jem.20101812 PubMedCentralPubMedGoogle Scholar
  241. 241.
    Qiao W, Chen L, Zhang M (2014) MicroRNA-205 regulates the calcification and osteoblastic differentiation of vascular smooth muscle cells. Cell Physiol Biochem 33(6):1945–1953. doi: 10.1159/000362971 PubMedGoogle Scholar
  242. 242.
    Jalali S, Ramanathan GK, Parthasarathy PT, Aljubran S, Galam L, Yunus A, Garcia S, Cox RR Jr, Lockey RF, Kolliputi N (2012) Mir-206 regulates pulmonary artery smooth muscle cell proliferation and differentiation. PLoS One 7(10):e46808. doi: 10.1371/journal.pone.0046808 PubMedCentralPubMedGoogle Scholar
  243. 243.
    Gou D, Ramchandran R, Peng X, Yao L, Kang K, Sarkar J, Wang Z, Zhou G, Raj JU (2012) miR-210 has an antiapoptotic effect in pulmonary artery smooth muscle cells during hypoxia. Am J Physiol Lung Cell Mol Physiol 303(8):L682–L691. doi: 10.1152/ajplung.00344.2011 PubMedCentralPubMedGoogle Scholar
  244. 244.
    Zhao H, Wen G, Huang Y, Yu X, Chen Q, Afzal TA, Luong LA, Zhu J, Shu Y, Zhang L, Xiao Q (2015) MicroRNA-22 regulates smooth muscle cell differentiation from stem cells by targeting methyl CpG-binding protein 2. Arterioscler Thromb Vasc Biol. doi: 10.1161/ATVBAHA.114.305212 Google Scholar
  245. 245.
    Liu X, Cheng Y, Chen X, Yang J, Xu L, Zhang C (2011) MicroRNA-31 regulated by the extracellular regulated kinase is involved in vascular smooth muscle cell growth via large tumor suppressor homolog 2. J Biol Chem 286(49):42371–42380. doi: 10.1074/jbc.M111.261065 PubMedCentralPubMedGoogle Scholar
  246. 246.
    Wang J, Yan CH, Li Y, Xu K, Tian XX, Peng CF, Tao J, Sun MY, Han YL (2013) MicroRNA-31 controls phenotypic modulation of human vascular smooth muscle cells by regulating its target gene cellular repressor of E1A-stimulated genes. Exp Cell Res 319(8):1165–1175. doi: 10.1016/j.yexcr.2013.03.010 PubMedGoogle Scholar
  247. 247.
    Merlet E, Atassi F, Motiani RK, Mougenot N, Jacquet A, Nadaud S, Capiod T, Trebak M, Lompre AM, Marchand A (2013) miR-424/322 regulates vascular smooth muscle cell phenotype and neointimal formation in the rat. Cardiovasc Res 98(3):458–468. doi: 10.1093/cvr/cvt045 PubMedCentralPubMedGoogle Scholar
  248. 248.
    Kim MH, Ham O, Lee SY, Choi E, Lee CY, Park JH, Lee J, Seo HH, Seung M, Choi E, Min PK, Hwang KC (2014) MicroRNA-365 inhibits the proliferation of vascular smooth muscle cells by targeting cyclin D1. J Cell Biochem 115(10):1752–1761. doi: 10.1002/jcb.24841 PubMedGoogle Scholar
  249. 249.
    Li P, Liu Y, Yi B, Wang G, You X, Zhao X, Summer R, Qin Y, Sun J (2013) MicroRNA-638 is highly expressed in human vascular smooth muscle cells and inhibits PDGF-BB-induced cell proliferation and migration through targeting orphan nuclear receptor NOR1. Cardiovasc Res 99(1):185–193. doi: 10.1093/cvr/cvt082 PubMedCentralPubMedGoogle Scholar
  250. 250.
    Li P, Zhu N, Yi B, Wang N, Chen M, You X, Zhao X, Solomides CC, Qin Y, Sun J (2013) MicroRNA-663 regulates human vascular smooth muscle cell phenotypic switch and vascular neointimal formation. Circ Res 113(10):1117–1127. doi: 10.1161/CIRCRESAHA.113.301306 PubMedCentralPubMedGoogle Scholar
  251. 251.
    Kim S, Hata A, Kang H (2014) Down-regulation of miR-96 by bone morphogenetic protein signaling is critical for vascular smooth muscle cell phenotype modulation. J Cell Biochem 115(5):889–895. doi: 10.1002/jcb.24730 PubMedGoogle Scholar
  252. 252.
    Cao H, Hu X, Zhang Q, Wang J, Li J, Liu B, Shao Y, Li X, Zhang J, Xin S (2014) Upregulation of let-7a inhibits vascular smooth muscle cell proliferation in vitro and in vein graft intimal hyperplasia in rats. J Surg Res 192(1):223–233. doi: 10.1016/j.jss.2014.05.045 PubMedGoogle Scholar
  253. 253.
    Hassel D, Cheng P, White MP, Ivey KN, Kroll J, Augustin HG, Katus HA, Stainier DY, Srivastava D (2012) MicroRNA-10 regulates the angiogenic behavior of zebrafish and human endothelial cells by promoting vascular endothelial growth factor signaling. Circ Res 111(11):1421–1433. doi: 10.1161/CIRCRESAHA.112.279711 PubMedCentralPubMedGoogle Scholar
  254. 254.
    Grundmann S, Hans FP, Kinniry S, Heinke J, Helbing T, Bluhm F, Sluijter JP, Hoefer I, Pasterkamp G, Bode C, Moser M (2011) MicroRNA-100 regulates neovascularization by suppression of mammalian target of rapamycin in endothelial and vascular smooth muscle cells. Circulation 123(9):999–1009. doi: 10.1161/CIRCULATIONAHA.110.000323 PubMedGoogle Scholar
  255. 255.
    Meng S, Cao J, Wang L, Zhou Q, Li Y, Shen C, Zhang X, Wang C (2012) MicroRNA 107 partly inhibits endothelial progenitor cells differentiation via HIF-1beta. PLoS One 7(7):e40323. doi: 10.1371/journal.pone.0040323 PubMedCentralPubMedGoogle Scholar
  256. 256.
    Schober A, Nazari-Jahantigh M, Wei Y, Bidzhekov K, Gremse F, Grommes J, Megens RT, Heyll K, Noels H, Hristov M, Wang S, Kiessling F, Olson EN, Weber C (2014) MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1. Nat Med 20(4):368–376. doi: 10.1038/nm.3487 PubMedCentralPubMedGoogle Scholar
  257. 257.
    Chen Y, Gorski DH (2008) Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood 111(3):1217–1226. doi: 10.1182/blood-2007-07-104133 PubMedCentralPubMedGoogle Scholar
  258. 258.
    Anand S, Majeti BK, Acevedo LM, Murphy EA, Mukthavaram R, Scheppke L, Huang M, Shields DJ, Lindquist JN, Lapinski PE, King PD, Weis SM, Cheresh DA (2010) MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis. Nat Med 16(8):909–914. doi: 10.1038/nm.2186 PubMedCentralPubMedGoogle Scholar
  259. 259.
    Cheng HS, Sivachandran N, Lau A, Boudreau E, Zhao JL, Baltimore D, Delgado-Olguin P, Cybulsky MI, Fish JE (2013) MicroRNA-146 represses endothelial activation by inhibiting pro-inflammatory pathways. EMBO Mol Med 5(7):949–966. doi: 10.1002/emmm.201202318 PubMedCentralPubMedGoogle Scholar
  260. 260.
    Chatterjee V, Beard RS Jr, Reynolds JJ, Haines R, Guo M, Rubin M, Guido J, Wu MH, Yuan SY (2014) MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression. PLoS One 9(10):e110286. doi: 10.1371/journal.pone.0110286 PubMedCentralPubMedGoogle Scholar
  261. 261.
    Chamorro-Jorganes A, Araldi E, Rotllan N, Cirera-Salinas D, Suarez Y (2014) Autoregulation of glypican-1 by intronic microRNA-149 fine tunes the angiogenic response to FGF2 in human endothelial cells. J Cell Sci 127(Pt 6):1169–1178. doi: 10.1242/jcs.130518 PubMedCentralPubMedGoogle Scholar
  262. 262.
    Yin KJ, Olsen K, Hamblin M, Zhang J, Schwendeman SP, Chen YE (2012) Vascular endothelial cell-specific microRNA-15a inhibits angiogenesis in hindlimb ischemia. J Biol Chem 287(32):27055–27064. doi: 10.1074/jbc.M112.364414 PubMedCentralPubMedGoogle Scholar
  263. 263.
    Wu Y, Huang A, Li T, Su X, Ding H, Li H, Qin X, Hou L, Zhao Q, Ge X, Fang T, Wang R, Gao C, Li J, Shao N (2014) MiR-152 reduces human umbilical vein endothelial cell proliferation and migration by targeting ADAM17. FEBS Lett 588(12):2063–2069. doi: 10.1016/j.febslet.2014.04.037 PubMedGoogle Scholar
  264. 264.
    Sun HX, Zeng DY, Li RT, Pang RP, Yang H, Hu YL, Zhang Q, Jiang Y, Huang LY, Tang YB, Yan GJ, Zhou JG (2012) Essential role of microRNA-155 in regulating endothelium-dependent vasorelaxation by targeting endothelial nitric oxide synthase. Hypertension 60(6):1407–1414. doi: 10.1161/HYPERTENSIONAHA.112.197301 PubMedGoogle Scholar
  265. 265.
    Pulkkinen KH, Yla-Herttuala S, Levonen AL (2011) Heme oxygenase 1 is induced by miR-155 via reduced BACH1 translation in endothelial cells. Free Radic Biol Med 51(11):2124–2131. doi: 10.1016/j.freeradbiomed.2011.09.014 PubMedGoogle Scholar
  266. 266.
    Yin R, Wang R, Guo L, Zhang W, Lu Y (2013) MiR-17-3p inhibits angiogenesis by downregulating flk-1 in the cell growth signal pathway. J Vasc Res 50(2):157–166. doi: 10.1159/000345697 PubMedGoogle Scholar
  267. 267.
    Kazenwadel J, Michael MZ, Harvey NL (2010) Prox1 expression is negatively regulated by miR-181 in endothelial cells. Blood 116(13):2395–2401. doi: 10.1182/blood-2009-12-256297 PubMedGoogle Scholar
  268. 268.
    Sun X, Icli B, Wara AK, Belkin N, He S, Kobzik L, Hunninghake GM, Vera MP, Registry M, Blackwell TS, Baron RM, Feinberg MW (2012) MicroRNA-181b regulates NF-kappaB-mediated vascular inflammation. J Clin Invest 122(6):1973–1990. doi: 10.1172/JCI61495 PubMedGoogle Scholar
  269. 269.
    Chan YC, Khanna S, Roy S, Sen CK (2011) miR-200b targets Ets-1 and is down-regulated by hypoxia to induce angiogenic response of endothelial cells. J Biol Chem 286(3):2047–2056. doi: 10.1074/jbc.M110.158790 PubMedCentralPubMedGoogle Scholar
  270. 270.
    Magenta A, Cencioni C, Fasanaro P, Zaccagnini G, Greco S, Sarra-Ferraris G, Antonini A, Martelli F, Capogrossi MC (2011) miR-200c is upregulated by oxidative stress and induces endothelial cell apoptosis and senescence via ZEB1 inhibition. Cell Death Differ 18(10):1628–1639. doi: 10.1038/cdd.2011.42 PubMedCentralPubMedGoogle Scholar
  271. 271.
    Luo Z, Wen G, Wang G, Pu X, Ye S, Xu Q, Wang W, Xiao Q (2013) MicroRNA-200C and -150 play an important role in endothelial cell differentiation and vasculogenesis by targeting transcription repressor ZEB1. Stem Cells 31(9):1749–1762. doi: 10.1002/stem.1448 PubMedGoogle Scholar
  272. 272.
    Weber M, Baker MB, Moore JP, Searles CD (2010) MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity. Biochem Biophys Res Commun 393(4):643–648. doi: 10.1016/j.bbrc.2010.02.045 PubMedCentralPubMedGoogle Scholar
  273. 273.
    Fasanaro P, D’Alessandra Y, Di Stefano V, Melchionna R, Romani S, Pompilio G, Capogrossi MC, Martelli F (2008) MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem 283(23):15878–15883. doi: 10.1074/jbc.M800731200 PubMedCentralPubMedGoogle Scholar
  274. 274.
    van Mil A, Grundmann S, Goumans MJ, Lei Z, Oerlemans MI, Jaksani S, Doevendans PA, Sluijter JP (2012) MicroRNA-214 inhibits angiogenesis by targeting Quaking and reducing angiogenic growth factor release. Cardiovasc Res 93(4):655–665. doi: 10.1093/cvr/cvs003 PubMedGoogle Scholar
  275. 275.
    Menghini R, Casagrande V, Cardellini M, Martelli E, Terrinoni A, Amati F, Vasa-Nicotera M, Ippoliti A, Novelli G, Melino G, Lauro R, Federici M (2009) MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1. Circulation 120(15):1524–1532. doi: 10.1161/CIRCULATIONAHA.109.864629 PubMedGoogle Scholar
  276. 276.
    Small EM, Sutherland LB, Rajagopalan KN, Wang S, Olson EN (2010) MicroRNA-218 regulates vascular patterning by modulation of Slit-Robo signaling. Circ Res 107(11):1336–1344. doi: 10.1161/CIRCRESAHA.110.227926 PubMedCentralPubMedGoogle Scholar
  277. 277.
    Chen Y, Banda M, Speyer CL, Smith JS, Rabson AB, Gorski DH (2010) Regulation of the expression and activity of the antiangiogenic homeobox gene GAX/MEOX2 by ZEB2 and microRNA-221. Mol Cell Biol 30(15):3902–3913. doi: 10.1128/MCB.01237-09 PubMedCentralPubMedGoogle Scholar
  278. 278.
    Nicoli S, Knyphausen CP, Zhu LJ, Lakshmanan A, Lawson ND (2012) miR-221 is required for endothelial tip cell behaviors during vascular development. Dev Cell 22(2):418–429. doi: 10.1016/j.devcel.2012.01.008 PubMedCentralPubMedGoogle Scholar
  279. 279.
    Zhou Q, Gallagher R, Ufret-Vincenty R, Li X, Olson EN, Wang S (2011) Regulation of angiogenesis and choroidal neovascularization by members of microRNA-23~27~24 clusters. Proc Natl Acad Sci USA 108(20):8287–8292. doi: 10.1073/pnas.1105254108 PubMedCentralPubMedGoogle Scholar
  280. 280.
    Wang J, Wang Y, Wang Y, Ma Y, Lan Y, Yang X (2013) Transforming growth factor beta-regulated microRNA-29a promotes angiogenesis through targeting the phosphatase and tensin homolog in endothelium. J Biol Chem 288(15):10418–10426. doi: 10.1074/jbc.M112.444463 PubMedCentralPubMedGoogle Scholar
  281. 281.
    Bridge G, Monteiro R, Henderson S, Emuss V, Lagos D, Georgopoulou D, Patient R, Boshoff C (2012) The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis. Blood 120(25):5063–5072. doi: 10.1182/blood-2012-04-423004 PubMedGoogle Scholar
  282. 282.
    Ying C, Sui-Xin L, Kang-Ling X, Wen-Liang Z, Lei D, Yuan L, Fan Z, Chen Z (2014) MicroRNA-492 reverses high glucose-induced insulin resistance in HUVEC cells through targeting resistin. Mol Cell Biochem 391(1–2):117–125. doi: 10.1007/s11010-014-1993-7 PubMedCentralPubMedGoogle Scholar
  283. 283.
    Caporali A, Meloni M, Vollenkle C, Bonci D, Sala-Newby GB, Addis R, Spinetti G, Losa S, Masson R, Baker AH, Agami R, le Sage C, Condorelli G, Madeddu P, Martelli F, Emanueli C (2011) Deregulation of microRNA-503 contributes to diabetes mellitus-induced impairment of endothelial function and reparative angiogenesis after limb ischemia. Circulation 123(3):282–291. doi: 10.1161/CIRCULATIONAHA.110.952325 PubMedGoogle Scholar
  284. 284.
    Yoo JK, Kim J, Choi SJ, Noh HM, Kwon YD, Yoo H, Yi HS, Chung HM, Kim JK (2012) Discovery and characterization of novel microRNAs during endothelial differentiation of human embryonic stem cells. Stem Cells Dev 21(11):2049–2057. doi: 10.1089/scd.2011.0500 PubMedCentralPubMedGoogle Scholar
  285. 285.
    Tang YY, Wo LK, Chai H (2013) Effects of noncoding RNA NRON gene regulation on human umbilical vein endothelial cells functions. Zhonghua xin xue guan bing za zhi 41(3):245–250PubMedGoogle Scholar
  286. 286.
    Bianchessi V, Badi I, Bertolotti M, Nigro P, D’Alessandra Y, Capogrossi MC, Zanobini M, Pompilio G, Raucci A, Lauri A (2015) The mitochondrial lncRNA ASncmtRNA-2 is induced in aging and replicative senescence in Endothelial Cells. J Mol Cell Cardiol 81:62–70. doi: 10.1016/j.yjmcc.2015.01.012 PubMedGoogle Scholar
  287. 287.
    Wang J, Chen L, Li H, Yang J, Gong Z, Wang B, Zhao X (2015) Clopidogrel reduces apoptosis and promotes proliferation of human vascular endothelial cells induced by palmitic acid via suppression of the long non-coding RNA HIF1A-AS1 in vitro. Mol Cell Biochem. doi: 10.1007/s11010-015-2379-1 Google Scholar

Copyright information

© Springer Basel 2015

Authors and Affiliations

  1. 1.Aab Cardiovascular Research InstituteUniversity of Rochester School of Medicine and DentistryRochesterUSA
  2. 2.Center for Cardiovascular SciencesAlbany Medical CollegeAlbanyUSA

Personalised recommendations