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Regulation of angiogenesis by microRNAs in cardiovascular diseases

Abstract

Non-coding RNAs are functional RNA molecules comprising the majority of human transcriptome. Only about 1.5% of the human genome is transcribed into messenger RNAs (mRNA) that are translated into proteins. Among the non-coding RNAs, miRNAs are extensively studied and miR targets in endothelial cells, perivascular cells, and angiogenic signaling are relatively well defined. MicroRNAs not only regulate transcripts in situ but also function as paracrine mediators in affecting angiogenesis at distant sites. Exosomal miRs are implicated in modulating endothelial cell function and angiogenesis. Thus miRs have been shown to affect tissue microenvironment in a multitude of ways. A comprehensive analysis of the role of miRs in modulation of angiogenesis and their impact on cardiovascular diseases is presented in this review.

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References

  1. 1.

    Daugaard I, Hansen TB (2017) Biogenesis and function of Ago-associated RNAs. Trends Genet 33(3):208–219. https://doi.org/10.1016/j.tig.2017.01.003

  2. 2.

    Morin RD, O’Connor MD, Griffith M, Kuchenbauer F, Delaney A, Prabhu AL, Zhao Y, McDonald H, Zeng T, Hirst M, Eaves CJ, Marra MA (2008) Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells. Genome Res 18(4):610–621. https://doi.org/10.1101/gr.7179508

  3. 3.

    Cui L, Nakano K, Obchoei S, Setoguchi K, Matsumoto M, Yamamoto T, Obika S, Shimada K, Hiraoka N (2017) Small nucleolar noncoding RNA SNORA23, up-regulated in human pancreatic ductal adenocarcinoma, regulates expression of spectrin repeat-containing nuclear envelope 2 to promote growth and metastasis of xenograft tumors in mice. Gastroenterology 153(1):292–306 e292. https://doi.org/10.1053/j.gastro.2017.03.050

  4. 4.

    Kondo A, Nonaka A, Shimamura T, Yamamoto S, Yoshida T, Kodama T, Aburatani H, Osawa T (2017) Long noncoding RNA JHDM1D-AS1 promotes tumor growth by regulating angiogenesis in response to nutrient starvation. Mol Cell Biol. https://doi.org/10.1128/MCB.00125-17

  5. 5.

    Zhan R, Xu K, Pan J, Xu Q, Xu S, Shen J (2017) Long noncoding RNA MEG3 mediated angiogenesis after cerebral infarction through regulating p53/NOX4 axis. Biochem Biophys Res Commun 490(3):700–706. https://doi.org/10.1016/j.bbrc.2017.06.104

  6. 6.

    Zhang CY, Yu MS, Li X, Zhang Z, Han CR, Yan B (2017) Overexpression of long non-coding RNA MEG3 suppresses breast cancer cell proliferation, invasion, and angiogenesis through AKT pathway. Tumour Biol 39(6):1010428317701311. https://doi.org/10.1177/1010428317701311

  7. 7.

    Gong L, Xu H, Chang H, Tong Y, Zhang T, Guo G (2018) Knockdown of long non-coding RNA MEG3 protects H9c2 cells from hypoxia-induced injury by targeting microRNA-183. J Cell Biochem 119(2):1429–1440. https://doi.org/10.1002/jcb.26304

  8. 8.

    Leisegang MS, Fork C, Josipovic I, Richter FM, Preussner J, Hu J, Miller MJ, Epah J, Hofmann P, Gunther S, Moll F, Valasarajan C, Heidler J, Ponomareva Y, Freiman TM, Maegdefessel L, Plate KH, Mittelbronn M, Uchida S, Kunne C, Stellos K, Schermuly RT, Weissmann N, Devraj K, Wittig I, Boon RA, Dimmeler S, Pullamsetti SS, Looso M, Miller FJ Jr, Brandes RP (2017) Long noncoding RNA MANTIS facilitates endothelial angiogenic function. Circulation 136(1):65–79. https://doi.org/10.1161/CIRCULATIONAHA.116.026991

  9. 9.

    Man HSJ, Sukumar AN, Lam GC, Turgeon PJ, Yan MS, Ku KH, Dubinsky MK, Ho JJD, Wang JJ, Das S, Mitchell N, Oettgen P, Sefton MV, Marsden PA (2018) Angiogenic patterning by STEEL, an endothelial-enriched long noncoding RNA. Proc Natl Acad Sci USA 115(10):2401–2406. https://doi.org/10.1073/pnas.1715182115

  10. 10.

    Haemmig S, Simion V, Yang D, Deng Y, Feinberg MW (2017) Long noncoding RNAs in cardiovascular disease, diagnosis, and therapy. Curr Opin Cardiol 32(6):776–783. https://doi.org/10.1097/HCO.0000000000000454

  11. 11.

    Yu D, Tang C, Liu P, Qian W, Sheng L (2018) Targeting lncRNAs for cardiovascular therapeutics in coronary artery disease. Curr Pharm Des. https://doi.org/10.2174/1381612824666180108120727

  12. 12.

    Ong SB, Katwadi K, Kwek XY, Ismail NI, Chinda K, Ong SG, Hausenloy DJ (2018) Non-coding RNAs as therapeutic targets for preventing myocardial ischemia-reperfusion injury. Expert Opin Ther Targets 22(3):247–261. https://doi.org/10.1080/14728222.2018.1439015

  13. 13.

    Bao MH, Szeto V, Yang BB, Zhu SZ, Sun HS, Feng ZP (2018) Long non-coding RNAs in ischemic stroke. Cell Death Dis 9(3):281. https://doi.org/10.1038/s41419-018-0282-x

  14. 14.

    Hou J, Wang L, Wu Q, Zheng G, Long H, Wu H, Zhou C, Guo T, Zhong T, Wang L, Chen X, Wang T (2018) Long noncoding RNA H19 upregulates vascular endothelial growth factor A to enhance mesenchymal stem cells survival and angiogenic capacity by inhibiting miR-199a-5p. Stem Cell Res Ther 9(1):109. https://doi.org/10.1186/s13287-018-0861-x

  15. 15.

    van Balkom BW, Eisele AS, Pegtel DM, Bervoets S, Verhaar MC (2015) Quantitative and qualitative analysis of small RNAs in human endothelial cells and exosomes provides insights into localized RNA processing, degradation and sorting. J Extracell Vesicles 4:26760. https://doi.org/10.3402/jev.v4.26760

  16. 16.

    Umezu T, Tadokoro H, Azuma K, Yoshizawa S, Ohyashiki K, Ohyashiki JH (2014) Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1. Blood 124(25):3748–3757. https://doi.org/10.1182/blood-2014-05-576116

  17. 17.

    Hsu YL, Hung JY, Chang WA, Lin YS, Pan YC, Tsai PH, Wu CY, Kuo PL (2017) Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1. Oncogene 36(34):4929–4942. https://doi.org/10.1038/onc.2017.105

  18. 18.

    Ye SB, Zhang H, Cai TT, Liu YN, Ni JJ, He J, Peng JY, Chen QY, Mo HY, Jun C, Zhang XS, Zeng YX, Li J (2016) Exosomal miR-24-3p impedes T-cell function by targeting FGF11 and serves as a potential prognostic biomarker for nasopharyngeal carcinoma. J Pathol 240(3):329–340. https://doi.org/10.1002/path.4781

  19. 19.

    van Beijnum JR, Giovannetti E, Poel D, Nowak-Sliwinska P, Griffioen AW (2017) miRNAs: micro-managers of anticancer combination therapies. Angiogenesis 20(2):269–285. https://doi.org/10.1007/s10456-017-9545-x

  20. 20.

    Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70

  21. 21.

    Ware JA, Simons M (1997) Angiogenesis in ischemic heart disease. Nat Med 3(2):158–164

  22. 22.

    Yang WJ, Yang DD, Na S, Sandusky GE, Zhang Q, Zhao G (2005) Dicer is required for embryonic angiogenesis during mouse development. J Biol Chem 280(10):9330–9335. https://doi.org/10.1074/jbc.M413394200

  23. 23.

    Hedman M, Hartikainen J, Syvanne M, Stjernvall J, Hedman A, Kivela A, Vanninen E, Mussalo H, Kauppila E, Simula S, Narvanen O, Rantala A, Peuhkurinen K, Nieminen MS, Laakso M, Yla-Herttuala S (2003) Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia: phase II results of the Kuopio Angiogenesis Trial (KAT). Circulation 107(21):2677–2683. https://doi.org/10.1161/01.CIR.0000070540.80780.92

  24. 24.

    Henry TD, Annex BH, McKendall GR, Azrin MA, Lopez JJ, Giordano FJ, Shah PK, Willerson JT, Benza RL, Berman DS, Gibson CM, Bajamonde A, Rundle AC, Fine J, McCluskey ER, Investigators V (2003) The VIVA trial: vascular endothelial growth factor in ischemia for vascular angiogenesis. Circulation 107(10):1359–1365

  25. 25.

    Simons M, Annex BH, Laham RJ, Kleiman N, Henry T, Dauerman H, Udelson JE, Gervino EV, Pike M, Whitehouse MJ, Moon T, Chronos NA (2002) Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2: double-blind, randomized, controlled clinical trial. Circulation 105(7):788–793

  26. 26.

    Azzouzi HE, Leptidis S, Doevendans PA, De Windt LJ (2015) HypoxamiRs: regulators of cardiac hypoxia and energy metabolism. Trends Endocrinol Metab 26(9):502–508. https://doi.org/10.1016/j.tem.2015.06.008

  27. 27.

    Nguyen MA, Karunakaran D, Rayner KJ (2014) Unlocking the door to new therapies in cardiovascular disease: microRNAs hold the key. Curr Cardiol Rep 16(11):539. https://doi.org/10.1007/s11886-014-0539-7

  28. 28.

    Welten SM, Bastiaansen AJ, de Jong RC, de Vries MR, Peters EA, Boonstra MC, Sheikh SP, La Monica N, Kandimalla ER, Quax PH, Nossent AY (2014) Inhibition of 14q32 MicroRNAs miR-329, miR-487b, miR-494, and miR-495 increases neovascularization and blood flow recovery after ischemia. Circ Res 115(8):696–708. https://doi.org/10.1161/CIRCRESAHA.114.304747

  29. 29.

    Nossent AY, Eskildsen TV, Andersen LB, Bie P, Bronnum H, Schneider M, Andersen DC, Welten SM, Jeppesen PL, Hamming JF, Hansen JL, Quax PH, Sheikh SP (2013) The 14q32 microRNA-487b targets the antiapoptotic insulin receptor substrate 1 in hypertension-induced remodeling of the aorta. Ann Surg 258(5):743–751. https://doi.org/10.1097/SLA.0b013e3182a6aac0. (discussion 752–743).

  30. 30.

    Martinez-Micaelo N, Beltran-Debon R, Aragones G, Faiges M, Alegret JM (2017) MicroRNAs clustered within the 14q32 locus are associated with endothelial damage and microparticle secretion in bicuspid aortic valve disease. Front Physiol 8:648. https://doi.org/10.3389/fphys.2017.00648

  31. 31.

    Gonzalez-Vallinas M, Rodriguez-Paredes M, Albrecht M, Sticht C, Stichel D, Gutekunst J, Pitea A, Sass S, Sanchez-Rivera FJ, Lorenzo-Bermejo J, Schmitt J, De La Torre C, Warth A, Theis FJ, Muller NS, Gretz N, Muley T, Meister M, Tschaharganeh DF, Schirmacher P, Matthaus F, Breuhahn K (2018) Epigenetically regulated chromosome 14q32 miRNA cluster induces metastasis and predicts poor prognosis in lung adenocarcinoma patients. Mol Cancer Res 16(3):390–402. https://doi.org/10.1158/1541-7786.MCR-17-0334

  32. 32.

    Kameswaran V, Bramswig NC, McKenna LB, Penn M, Schug J, Hand NJ, Chen Y, Choi I, Vourekas A, Won KJ, Liu C, Vivek K, Naji A, Friedman JR, Kaestner KH (2014) Epigenetic regulation of the DLK1-MEG3 microRNA cluster in human type 2 diabetic islets. Cell Metab 19(1):135–145. https://doi.org/10.1016/j.cmet.2013.11.016

  33. 33.

    Sucharov C, Bristow MR, Port JD (2008) miRNA expression in the failing human heart: functional correlates. J Mol Cell Cardiol 45(2):185–192. https://doi.org/10.1016/j.yjmcc.2008.04.014

  34. 34.

    Gavin JB, Maxwell L, Edgar SG (1998) Microvascular involvement in cardiac pathology. J Mol Cell Cardiol 30(12):2531–2540. https://doi.org/10.1006/jmcc.1998.0824

  35. 35.

    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. https://doi.org/10.1161/CIRCULATIONAHA.110.000323

  36. 36.

    Wang FZ, Weber F, Croce C, Liu CG, Liao X, Pellett PE (2008) Human cytomegalovirus infection alters the expression of cellular microRNA species that affect its replication. J Virol 82(18):9065–9074. https://doi.org/10.1128/JVI.00961-08

  37. 37.

    Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, Furth EE, Lee WM, Enders GH, Mendell JT, Thomas-Tikhonenko A (2006) Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet 38(9):1060–1065. https://doi.org/10.1038/ng1855

  38. 38.

    Du P, Wang L, Sliz P, Gregory RI (2015) A biogenesis step upstream of microprocessor controls miR-17 approximately 92 expression. Cell 162(4):885–899. https://doi.org/10.1016/j.cell.2015.07.008

  39. 39.

    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. https://doi.org/10.1126/science.1174381

  40. 40.

    Bellera N, Barba I, Rodriguez-Sinovas A, Ferret E, Asin MA, Gonzalez-Alujas MT, Perez-Rodon J, Esteves M, Fonseca C, Toran N, Garcia Del Blanco B, Perez A, Garcia-Dorado D (2014) Single intracoronary injection of encapsulated antagomir-92a promotes angiogenesis and prevents adverse infarct remodeling. J Am Heart Assoc 3(5):e000946. https://doi.org/10.1161/JAHA.114.000946

  41. 41.

    Hinkel R, Penzkofer D, Zuhlke S, Fischer A, Husada W, Xu QF, Baloch E, van Rooij E, Zeiher AM, Kupatt C, Dimmeler S (2013) Inhibition of microRNA-92a protects against ischemia/reperfusion injury in a large-animal model. Circulation 128(10):1066–1075. https://doi.org/10.1161/CIRCULATIONAHA.113.001904

  42. 42.

    van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, Hill JA, Olson EN (2008) Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci USA 105(35):13027–13032. https://doi.org/10.1073/pnas.0805038105

  43. 43.

    Aurora AB, Mahmoud AI, Luo X, Johnson BA, van Rooij E, Matsuzaki S, Humphries KM, Hill JA, Bassel-Duby R, Sadek HA, Olson EN (2012) MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca(2)(+) overload and cell death. J Clin Invest 122(4):1222–1232. https://doi.org/10.1172/JCI59327

  44. 44.

    Shiojima I, Sato K, Izumiya Y, Schiekofer S, Ito M, Liao R, Colucci WS, Walsh K (2005) Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure. J Clin Invest 115(8):2108–2118. https://doi.org/10.1172/JCI24682

  45. 45.

    Duan Q, Yang L, Gong W, Chaugai S, Wang F, Chen C, Wang P, Zou MH, Wang DW (2015) MicroRNA-214 Is upregulated in heart failure patients and suppresses XBP1-mediated endothelial cells angiogenesis. J Cell Physiol 230(8):1964–1973. https://doi.org/10.1002/jcp.24942

  46. 46.

    Ghosh R, Lipson KL, Sargent KE, Mercurio AM, Hunt JS, Ron D, Urano F (2010) Transcriptional regulation of VEGF-A by the unfolded protein response pathway. PLoS ONE 5(3):e9575. https://doi.org/10.1371/journal.pone.0009575

  47. 47.

    Pereira ER, Liao N, Neale GA, Hendershot LM (2010) Transcriptional and post-transcriptional regulation of proangiogenic factors by the unfolded protein response. PLoS ONE. https://doi.org/10.1371/journal.pone.0012521

  48. 48.

    Copland IB (2011) Mesenchymal stromal cells for cardiovascular disease. J Cardiovasc Dis Res 2(1):3–13. https://doi.org/10.4103/0975-3583.78581

  49. 49.

    Wen Z, Huang W, Feng Y, Cai W, Wang Y, Wang X, Liang J, Wani M, Chen J, Zhu P, Chen JM, Millard RW, Fan GC, Wang Y (2014) MicroRNA-377 regulates mesenchymal stem cell-induced angiogenesis in ischemic hearts by targeting VEGF. PLoS ONE 9(9):e104666. https://doi.org/10.1371/journal.pone.0104666

  50. 50.

    David L, Feige JJ, Bailly S (2009) Emerging role of bone morphogenetic proteins in angiogenesis. Cytokine Growth Factor Rev 20(3):203–212. https://doi.org/10.1016/j.cytogfr.2009.05.001

  51. 51.

    Lechleider RJ, Ryan JL, Garrett L, Eng C, Deng C, Wynshaw-Boris A, Roberts AB (2001) Targeted mutagenesis of Smad1 reveals an essential role in chorioallantoic fusion. Dev Biol 240(1):157–167. https://doi.org/10.1006/dbio.2001.0469

  52. 52.

    Icli B, Wara AK, Moslehi J, Sun X, Plovie E, Cahill M, Marchini JF, Schissler A, Padera RF, Shi J, Cheng HW, Raghuram S, Arany Z, Liao R, Croce K, MacRae C, Feinberg MW (2013) MicroRNA-26a regulates pathological and physiological angiogenesis by targeting BMP/SMAD1 signaling. Circ Res 113(11):1231–1241. https://doi.org/10.1161/CIRCRESAHA.113.301780

  53. 53.

    Pankratz F, Bemtgen X, Zeiser R, Leonhardt F, Kreuzaler S, Hilgendorf I, Smolka C, Helbing T, Hoefer I, Esser JS, Kustermann M, Moser M, Bode C, Grundmann S (2015) MicroRNA-155 exerts cell-specific antiangiogenic but proarteriogenic effects during adaptive neovascularization. Circulation 131(18):1575–1589. https://doi.org/10.1161/CIRCULATIONAHA.114.014579

  54. 54.

    Fiedler J, Jazbutyte V, Kirchmaier BC, Gupta SK, Lorenzen J, Hartmann D, Galuppo P, Kneitz S, Pena JT, Sohn-Lee C, Loyer X, Soutschek J, Brand T, Tuschl T, Heineke J, Martin U, Schulte-Merker S, Ertl G, Engelhardt S, Bauersachs J, Thum T (2011) MicroRNA-24 regulates vascularity after myocardial infarction. Circulation 124(6):720–730. https://doi.org/10.1161/CIRCULATIONAHA.111.039008

  55. 55.

    Meloni M, Marchetti M, Garner K, Littlejohns B, Sala-Newby G, Xenophontos N, Floris I, Suleiman MS, Madeddu P, Caporali A, Emanueli C (2013) Local inhibition of microRNA-24 improves reparative angiogenesis and left ventricle remodeling and function in mice with myocardial infarction. Mol Ther 21(7):1390–1402. https://doi.org/10.1038/mt.2013.89

  56. 56.

    Qian L, Van Laake LW, Huang Y, Liu S, Wendland MF, Srivastava D (2011) miR-24 inhibits apoptosis and represses Bim in mouse cardiomyocytes. J Exp Med 208(3):549–560. https://doi.org/10.1084/jem.20101547

  57. 57.

    Leistner DM, Fischer-Rasokat U, Honold J, Seeger FH, Schachinger V, Lehmann R, Martin H, Burck I, Urbich C, Dimmeler S, Zeiher AM, Assmus B (2011) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI): final 5-year results suggest long-term safety and efficacy. Clin Res Cardiol 100(10):925–934. https://doi.org/10.1007/s00392-011-0327-y

  58. 58.

    Fadini GP, Agostini C, Avogaro A (2010) Autologous stem cell therapy for peripheral arterial disease meta-analysis and systematic review of the literature. Atherosclerosis 209(1):10–17. https://doi.org/10.1016/j.atherosclerosis.2009.08.033

  59. 59.

    Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, Zeiher AM, Dimmeler S (2001) Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89(1):E1–E7

  60. 60.

    Spinetti G, Fortunato O, Caporali A, Shantikumar S, Marchetti M, Meloni M, Descamps B, Floris I, Sangalli E, Vono R, Faglia E, Specchia C, Pintus G, Madeddu P, Emanueli C (2013) MicroRNA-15a and microRNA-16 impair human circulating proangiogenic cell functions and are increased in the proangiogenic cells and serum of patients with critical limb ischemia. Circ Res 112(2):335–346. https://doi.org/10.1161/CIRCRESAHA.111.300418

  61. 61.

    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. https://doi.org/10.1161/CIRCULATIONAHA.110.952325

  62. 62.

    Caporali A, Emanueli C (2011) MicroRNA-503 and the extended microRNA-16 family in angiogenesis. Trends Cardiovasc Med 21(6):162–166. https://doi.org/10.1016/j.tcm.2012.05.003

  63. 63.

    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. https://doi.org/10.1074/jbc.M112.364414

  64. 64.

    Chamorro-Jorganes A, Araldi E, Penalva LO, Sandhu D, Fernandez-Hernando C, Suarez Y (2011) MicroRNA-16 and microRNA-424 regulate cell-autonomous angiogenic functions in endothelial cells via targeting vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1. Arterioscler Thromb Vasc Biol 31(11):2595–2606. https://doi.org/10.1161/ATVBAHA.111.236521

  65. 65.

    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):272–284. https://doi.org/10.1016/j.devcel.2008.07.008

  66. 66.

    Wang S, Aurora AB, Johnson BA, Qi X, McAnally 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(2):261–271. https://doi.org/10.1016/j.devcel.2008.07.002

  67. 67.

    Jakob P, Doerries C, Briand S, Mocharla P, Krankel N, Besler C, Mueller M, Manes C, Templin C, Baltes C, Rudin M, Adams H, Wolfrum M, Noll G, Ruschitzka F, Luscher TF, Landmesser U (2012) Loss of angiomiR-126 and 130a in angiogenic early outgrowth cells from patients with chronic heart failure: role for impaired in vivo neovascularization and cardiac repair capacity. Circulation 126(25):2962–2975. https://doi.org/10.1161/CIRCULATIONAHA.112.093906

  68. 68.

    Yamakuchi M, Lotterman CD, Bao C, Hruban RH, Karim B, Mendell JT, Huso D, Lowenstein CJ (2010) P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis. Proc Natl Acad Sci USA 107(14):6334–6339. https://doi.org/10.1073/pnas.0911082107

  69. 69.

    Kim HW, Haider HK, Jiang S, Ashraf M (2009) Ischemic preconditioning augments survival of stem cells via miR-210 expression by targeting caspase-8-associated protein 2. J Biol Chem 284(48):33161–33168. https://doi.org/10.1074/jbc.M109.020925

  70. 70.

    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. https://doi.org/10.1074/jbc.M800731200

  71. 71.

    Song H, Zhang Z, Wang L (2008) Small interference RNA against PTP-1B reduces hypoxia/reoxygenation induced apoptosis of rat cardiomyocytes. Apoptosis 13(3):383–393. https://doi.org/10.1007/s10495-008-0181-1

  72. 72.

    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. https://doi.org/10.1172/JCI42980

  73. 73.

    Semo J, Sharir R, Afek A, Avivi C, Barshack I, Maysel-Auslender S, Krelin Y, Kain D, Entin-Meer M, Keren G, George J (2014) The 106b approximately 25 microRNA cluster is essential for neovascularization after hindlimb ischaemia in mice. Eur Heart J 35(45):3212–3223. https://doi.org/10.1093/eurheartj/eht041

  74. 74.

    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. https://doi.org/10.1073/pnas.1105254108

  75. 75.

    Biyashev D, Veliceasa D, Topczewski J, Topczewska JM, Mizgirev I, Vinokour E, Reddi AL, Licht JD, Revskoy SY, Volpert OV (2012) miR-27b controls venous specification and tip cell fate. Blood 119(11):2679–2687. https://doi.org/10.1182/blood-2011-07-370635

  76. 76.

    Veliceasa D, Biyashev D, Qin G, Misener S, Mackie AR, Kishore R, Volpert OV (2015) Therapeutic manipulation of angiogenesis with miR-27b. Vasc Cell 7:6. https://doi.org/10.1186/s13221-015-0031-1

  77. 77.

    Lei Z, van Mil A, Brandt MM, Grundmann S, Hoefer I, Smits M, El Azzouzi H, Fukao T, Cheng C, Doevendans PA, Sluijter JP (2015) MicroRNA-132/212 family enhances arteriogenesis after hindlimb ischaemia through modulation of the Ras-MAPK pathway. J Cell Mol Med 19(8):1994–2005. https://doi.org/10.1111/jcmm.12586

  78. 78.

    Deng Y, Larrivee B, Zhuang ZW, Atri D, Moraes F, Prahst C, Eichmann A, Simons M (2013) Endothelial RAF1/ERK activation regulates arterial morphogenesis. Blood 121(19):3988–3996. https://doi.org/10.1182/blood-2012-12-474601

  79. 79.

    Fitzgerald K, White S, Borodovsky A, Bettencourt BR, Strahs A, Clausen V, Wijngaard P, Horton JD, Taubel J, Brooks A, Fernando C, Kauffman RS, Kallend D, Vaishnaw A, Simon A (2017) A highly durable RNAi therapeutic inhibitor of PCSK9. N Engl J Med 376(1):41–51. https://doi.org/10.1056/NEJMoa1609243

  80. 80.

    Calway T, Kim GH (2015) Harnessing the therapeutic potential of micrornas for cardiovascular disease. J Cardiovasc Pharmacol Ther 20(2):131–143. https://doi.org/10.1177/1074248414552902

  81. 81.

    Ling H (2016) Non-coding RNAs: therapeutic strategies and delivery systems. Adv Exp Med Biol 937:229–237. https://doi.org/10.1007/978-3-319-42059-2_12

  82. 82.

    Ling H, Fabbri M, Calin GA (2013) MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov 12(11):847–865. https://doi.org/10.1038/nrd4140

  83. 83.

    Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, van der Meer AJ, Patick AK, Chen A, Zhou Y, Persson R, King BD, Kauppinen S, Levin AA, Hodges MR (2013) Treatment of HCV infection by targeting microRNA. N Engl J Med 368(18):1685–1694. https://doi.org/10.1056/NEJMoa1209026

  84. 84.

    Kwekkeboom RF, Sluijter JP, van Middelaar BJ, Metz CH, Brans MA, Kamp O, Paulus WJ, Musters RJ (2016) Increased local delivery of antagomir therapeutics to the rodent myocardium using ultrasound and microbubbles. J Control Release 222:18–31. https://doi.org/10.1016/j.jconrel.2015.11.020

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Acknowledgements

This work was supported in part by the following grants from the NIH, DA007097, DA034582, and funds from the University of Miami, Sylvester Comprehensive Cancer Center.

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Correspondence to Devika Kir.

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Kir, D., Schnettler, E., Modi, S. et al. Regulation of angiogenesis by microRNAs in cardiovascular diseases. Angiogenesis 21, 699–710 (2018). https://doi.org/10.1007/s10456-018-9632-7

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Keywords

  • MicroRNA
  • Non-coding RNA
  • Angiogenesis
  • lncRNA
  • Cardiovascular
  • MI
  • Therapeutics