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Mechanical Regulation of Epigenetic Modifications in Vascular Biology and Pathobiology

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Vascular Mechanobiology in Physiology and Disease

Part of the book series: Cardiac and Vascular Biology ((Abbreviated title: Card. vasc. biol.,volume 8))

Abstract

Shear stress and cyclic stretch are mechanical forces on the vessel wall exerted by blood flow and luminal pressure. These forces regulate gene expression and function in vascular cells, including endothelial cells (ECs) and smooth muscle cells (SMCs), thus affecting vascular biology in health and pathobiology in disease. Epigenetics refers to the study of sequence-independent heritable DNA alterations that modulate gene expression, including DNA methylation, histone modification/chromatin remodeling, and RNA-based mechanisms. Recently, the roles of mechanical force-induced epigenetic modifications in vascular gene expression and function have been intensively investigated. This chapter presents a critical concept: vascular gene expression can be mechanically modulated without DNA sequence change. By elucidating the relationship between mechanical forces and epigenetic modifications in gene expression, cell proliferation, angiogenesis, migration, and pathological status, this review provides a conceptual framework for understanding how mechanical force-induced epigenetic modifications modulate gene expression and cellular function in vascular biology in health and pathobiology in disease. This review contributes to our knowledge of how the mechanical microenvironment affects epigenetic changes in vascular cells and modulates their functions and behaviors, with the consequent modulation in vascular diseases.

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Abbreviations

3′-UTR:

3′-Untranslated region

5mC:

5-Methylcytosine

ABs:

Apoptotic bodies

Ago:

Argonaute

AMPK:

AMP-activated protein kinase

ANRIL:

Antisense noncoding RNA at the Ink4 locus

ApoE–/–:

Apolipoprotein E-deficient genotype

BMP3:

Bone morphogenetic protein 3

CTGF:

Connective tissue growth factor

CVD:

Cardiovascular disease

DNMT:

DNA methyltransferase

EC:

Endothelial cell

ECM:

Extracellular matrix

EV:

Extracellular vesicle

eNOS:

Endothelial nitric oxide synthase

FAK:

Focal adhesion kinase

GAX:

Growth arrest-specific homeobox

GSK-3β:

Glycogen synthase kinase-3β

H:

Histone

HAT:

Histone acetyltransferase

HDAC:

Histone deacetylase

HUVEC:

Human umbilical vein endothelial cell

ICAM-1:

Intercellular adhesion molecule-1

IL:

Interleukin

IRAK:

IL-1 receptor-associated kinase

KLF:

KrĂĽppel-like factor

LISPR1:

Long intergenic noncoding RNA antisense to S1PR1

LncRNA:

Long noncoding RNA

MALAT1:

Metastasis-associated lung adenocarcinoma transcript 1

MBD:

Methyl CpG-binding domain protein

MCP-1:

Monocyte chemotactic protein-1

MEF2:

Myocyte enhancer factor 2

MiRNA:

MicroRNA

MiR-21:

MicroRNA-21

MMP:

Matrix metalloproteinase

mRNA:

Messenger RNA

mTOR:

Mammalian target of rapamycin

NAD:

Nicotinamide adenine dinucleotide

NcRNA:

Noncoding RNA

NF-κβ:

Nuclear factor-κβ

NO:

Nitric oxide

NQO1:

NADPH quinine oxidoreductase 1

Nrf2:

NF-E2-related factor 2

OSS:

Oscillatory shear stress

Ox-LDL:

Oxidized low-density lipoprotein

PPARα:

Peroxisome proliferator-activated receptor α

PRC:

Polycomb repressive complex

PRKD2:

Protein kinase D2

PSS:

Pulsatile shear stress

PTM:

Posttranslational modification

Rb:

Retinoblastoma protein

RNAi:

RNA interference

ROS:

Reactive oxygen species

S1P:

Sphingosine-1-phosphate

S1PR:

Sphingosine-1-phosphate receptor

SAM:

S-adenyl methionine

SHR:

Spontaneously hypertensive rat

SIRT:

Sirtuin

SMC:

Smooth muscle cell

STEEL:

Spliced-transcript endothelial-enriched lncRNA

TET:

Ten-eleven translocation methylcytosine dioxygenase

TNF-α:

Tumor necrosis factor

USS:

Unidirectional shear stress

VCAM-1:

Vascular cell adhesion molecule-1

VE-Cad:

VE-cadherin

VEGF:

Vascular endothelial growth factor

VEGFR2:

Vascular endothelial growth factor receptor 2

WKY:

Wistar Kyoto rat

References

  1. Butcher DT, Alliston T, Weaver VM (2009) A tense situation: forcing tumour progression. Nat Rev Cancer 9:108–122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chiu JJ, Chien S (2011) Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol Rev 91:327–387

    Article  PubMed  Google Scholar 

  3. Li YS, Haga JH, Chien S (2005) Molecular basis of the effects of shear stress on vascular endothelial cells. J Biomech 38:1949–1971

    Article  PubMed  Google Scholar 

  4. Jaalouk DE, Lammerding J (2009) Mechanotransduction gone awry. Nat Rev Mol Cell Biol 10:63–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hahn C, Schwartz MA (2009) Mechanotransduction in vascular physiology and atherogenesis. Nat Rev Mol Cell Biol 10:53–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Van Speybroeck L (2002) From epigenesis to epigenetics: the case of C. H. Waddington. Ann N Y Acad Sci 981:61–81

    Article  PubMed  Google Scholar 

  7. Singh S, Sonkar SK, Sonkar GK, Mahdi AA (2019) Diabetic kidney disease: a systematic review on the role of epigenetics as diagnostic and prognostic marker. Diabetes Metab Res Rev 35:e3155

    Article  PubMed  Google Scholar 

  8. Goldberg AD, Allis CD, Bernstein E (2007) Epigenetics: a landscape takes shape. Cell 128:635–638

    Article  CAS  PubMed  Google Scholar 

  9. Moore LD, Le T, Fan G (2013) DNA methylation and its basic function. Neuropsychopharmacology 38:23–38

    Article  CAS  PubMed  Google Scholar 

  10. Wu X, Zhang Y (2017) TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet 18:517–534

    Article  CAS  PubMed  Google Scholar 

  11. Winter J, Jung S, Keller S, Gregory RI, Diederichs S (2009) Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11:228–234

    Article  CAS  PubMed  Google Scholar 

  12. Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155–159

    Article  CAS  PubMed  Google Scholar 

  13. Sun M, Kraus WL (2015) From discovery to function: the expanding roles of long non-coding RNAs in physiology and disease. Endocr Rev 36:25–64

    Article  CAS  PubMed  Google Scholar 

  14. Man HJ, Yan MS, Lee JJ, Marsden PA (2016) Epigenetic determinants of cardiovascular gene expression: vascular endothelium. Epigenomics 8:959–979

    Article  CAS  PubMed  Google Scholar 

  15. Zoghbi HY, Beaudet AL (2016) Epigenetics and human disease. Cold Spring Harb Perspect Biol 8:a019497

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Alexander MR, Owens GK (2012) Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease. Annu Rev Physiol 74:13–40

    Article  CAS  PubMed  Google Scholar 

  17. Xu S, Pelisek J, Jin ZG (2018) Atherosclerosis is an epigenetic disease. Trends Endocrinol Metab 29:739–742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Mazzone R, Zwergel C, Artico M, Taurone S, Ralli M, Greco A, Mai A (2019) The emerging role of epigenetics in human autoimmune disorders. Clin Epigenetics 11:34

    Article  PubMed  PubMed Central  Google Scholar 

  19. Zhou B, Margariti A, Zeng L, Xu Q (2011) Role of histone deacetylases in vascular cell homeostasis and arteriosclerosis. Cardiovasc Res 90:413–420

    Article  CAS  PubMed  Google Scholar 

  20. Condorelli G, Latronico MV, Cavarretta E (2014) microRNAs in cardiovascular diseases: current knowledge and the road ahead. J Am Coll Cardiol 63:2177–2187

    Article  CAS  PubMed  Google Scholar 

  21. 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 34:2206–2216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Dunn J, Simmons R, Thabet S, Jo H (2015) The role of epigenetics in the endothelial cell shear stress response and atherosclerosis. Int J Biochem Cell Biol 67:167–176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ku DN, Giddens DP, Zarins CK, Glagov S (1985) Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis 5:293–302

    Article  CAS  PubMed  Google Scholar 

  24. Davies PF (1995) Flow-mediated endothelial mechanotransduction. Physiol Rev 75:519–560

    Article  CAS  PubMed  Google Scholar 

  25. Jufri NF, Mohamedali A, Avolio A, Baker MS (2015) Mechanical stretch: physiological and pathological implications for human vascular endothelial cells. Vasc Cell 7:8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Lu D, Kassab GS (2011) Role of shear stress and stretch in vascular mechanobiology. J R Soc Interface 8:1379–1385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hove JR, Koster RW, Forouhar AS, Acevedo-Bolton G, Fraser SE, Gharib M (2003) Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis. Nature 421:172–177

    Article  CAS  PubMed  Google Scholar 

  28. Boselli F, Vermot J (2016) Live imaging and modeling for shear stress quantification in the embryonic zebrafish heart. Methods 94:129–134

    Article  CAS  PubMed  Google Scholar 

  29. Huynh QK, McKinsey TA (2006) Protein kinase D directly phosphorylates histone deacetylase 5 via a random sequential kinetic mechanism. Arch Biochem Biophys 450:141–148

    Article  CAS  PubMed  Google Scholar 

  30. Banjo T, Grajcarek J, Yoshino D, Osada H, Miyasaka KY, Kida YS, Ueki Y, Nagayama K, Kawakami K, Matsumoto T et al (2013) Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21. Nat Commun 4:1978

    Article  PubMed  CAS  Google Scholar 

  31. Fernandez AP, Serrano J, Castro S, Salazar FJ, Lopez JC, Rodrigo J, Nava E (2003) Distribution of nitric oxide synthases and nitrotyrosine in the kidney of spontaneously hypertensive rats. J Hypertens 21:2375–2388

    Article  CAS  PubMed  Google Scholar 

  32. Yu J, deMuinck ED, Zhuang Z, Drinane M, Kauser K, Rubanyi GM, Qian HS, Murata T, Escalante B, Sessa WC (2005) Endothelial nitric oxide synthase is critical for ischemic remodeling, mural cell recruitment, and blood flow reserve. Proc Natl Acad Sci U S A 102:10999–11004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chien S (2007) Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell. Am J Physiol Heart Circ Physiol 292:H1209–H1224

    Article  CAS  PubMed  Google Scholar 

  34. Karino T, Goldsmith HL, Motomiya M, Mabuchi S, Sohara Y (1987) Flow patterns in vessels of simple and complex geometries. Ann N Y Acad Sci 516:422–441

    Article  CAS  PubMed  Google Scholar 

  35. Wang N, Miao H, Li YS, Zhang P, Haga JH, Hu Y, Young A, Yuan S, Nguyen P, Wu CC et al (2006) Shear stress regulation of Kruppel-like factor 2 expression is flow pattern-specific. Biochem Biophys Res Commun 341:1244–1251

    Article  CAS  PubMed  Google Scholar 

  36. Raffetto JD, Khalil RA (2008) Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease. Biochem Pharmacol 75:346–359

    Article  CAS  PubMed  Google Scholar 

  37. Shyy JY, Li YS, Lin MC, Chen W, Yuan S, Usami S, Chien S (1995) Multiple cis-elements mediate shear stress-induced gene expression. J Biomech 28:1451–1457

    Article  CAS  PubMed  Google Scholar 

  38. Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, Engelhardt B, Cao G, DeLisser H, Schwartz MA (2005) A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437:426–431

    Article  CAS  PubMed  Google Scholar 

  39. Chiu JJ, Wang DL, Chien S, Skalak R, Usami S (1998) Effects of disturbed flow on endothelial cells. J Biomech Eng 120:2–8

    Article  CAS  PubMed  Google Scholar 

  40. Chien S (2008) Effects of disturbed flow on endothelial cells. Ann Biomed Eng 36:554–562

    Article  PubMed  PubMed Central  Google Scholar 

  41. Matthews BD, Overby DR, Mannix R, Ingber DE (2006) Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels. J Cell Sci 119:508–518

    Article  CAS  PubMed  Google Scholar 

  42. Li S, Chen BP, Azuma N, Hu YL, Wu SZ, Sumpio BE, Shyy JY, Chien S (1999) Distinct roles for the small GTPases Cdc42 and Rho in endothelial responses to shear stress. J Clin Invest 103:1141–1150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Tzima E (2006) Role of small GTPases in endothelial cytoskeletal dynamics and the shear stress response. Circ Res 98:176–185

    Article  CAS  PubMed  Google Scholar 

  44. Galbraith CG, Skalak R, Chien S (1998) Shear stress induces spatial reorganization of the endothelial cell cytoskeleton. Cell Motil Cytoskeleton 40:317–330

    Article  CAS  PubMed  Google Scholar 

  45. Boon RA, Horrevoets AJ (2009) Key transcriptional regulators of the vasoprotective effects of shear stress. Hamostaseologie 29, 39–40, 41–43

    Google Scholar 

  46. Mohan S, Mohan N, Sprague EA (1997) Differential activation of NF-kappa B in human aortic endothelial cells conditioned to specific flow environments. Am J Physiol 273:C572–C578

    Article  CAS  PubMed  Google Scholar 

  47. Hosoya T, Maruyama A, Kang MI, Kawatani Y, Shibata T, Uchida K, Warabi E, Noguchi N, Itoh K, Yamamoto M (2005) Differential responses of the Nrf2-Keap1 system to laminar and oscillatory shear stresses in endothelial cells. J Biol Chem 280:27244–27250

    Article  CAS  PubMed  Google Scholar 

  48. Halka AT, Turner NJ, Carter A, Ghosh J, Murphy MO, Kirton JP, Kielty CM, Walker MG (2008) The effects of stretch on vascular smooth muscle cell phenotype in vitro. Cardiovasc Pathol 17:98–102

    Article  CAS  PubMed  Google Scholar 

  49. Qiu J, Zheng Y, Hu J, Liao D, Gregersen H, Deng X, Fan Y, Wang G (2014) Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding. J R Soc Interface 11:20130852

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Ramella M, Bertozzi G, Fusaro L, Talmon M, Manfredi M, Catoria MC, Casella F, Porta CM, Boldorini R, Fresu LG et al (2019) Effect of cyclic stretch on vascular endothelial cells and abdominal aortic aneurysm (AAA): role in the inflammatory response. Int J Mol Sci 20:287

    Article  PubMed Central  CAS  Google Scholar 

  51. Lemarie CA, Tharaux PL, Lehoux S (2010) Extracellular matrix alterations in hypertensive vascular remodeling. J Mol Cell Cardiol 48:433–439

    Article  CAS  PubMed  Google Scholar 

  52. Li C, Xu Q (2000) Mechanical stress-initiated signal transductions in vascular smooth muscle cells. Cell Signal 12:435–445

    Article  CAS  PubMed  Google Scholar 

  53. Haga JH, Li YS, Chien S (2007) Molecular basis of the effects of mechanical stretch on vascular smooth muscle cells. J Biomech 40:947–960

    Article  PubMed  Google Scholar 

  54. Birukov KG, Bardy N, Lehoux S, Merval R, Shirinsky VP, Tedgui A (1998) Intraluminal pressure is essential for the maintenance of smooth muscle caldesmon and filamin content in aortic organ culture. Arterioscler Thromb Vasc Biol 18:922–927

    Article  CAS  PubMed  Google Scholar 

  55. Verma RP, Hansch C (2007) Matrix metalloproteinases (MMPs): chemical-biological functions and (Q)SARs. Bioorg Med Chem 15:2223–2268

    Article  CAS  PubMed  Google Scholar 

  56. Asanuma K, Magid R, Johnson C, Nerem RM, Galis ZS (2003) Uniaxial strain upregulates matrix-degrading enzymes produced by human vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 284:H1778–H1784

    Article  CAS  PubMed  Google Scholar 

  57. Chapman GB, Durante W, Hellums JD, Schafer AI (2000) Physiological cyclic stretch causes cell cycle arrest in cultured vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 278:H748–H754

    Article  CAS  PubMed  Google Scholar 

  58. Liu XM, Ensenat D, Wang H, Schafer AI, Durante W (2003) Physiologic cyclic stretch inhibits apoptosis in vascular endothelium. FEBS Lett 541:52–56

    Article  CAS  PubMed  Google Scholar 

  59. Birukov KG, Jacobson JR, Flores AA, Ye SQ, Birukova AA, Verin AD, Garcia JG (2003) Magnitude-dependent regulation of pulmonary endothelial cell barrier function by cyclic stretch. Am J Physiol Lung Cell Mol Physiol 285:L785–L797

    Article  CAS  PubMed  Google Scholar 

  60. Pfisterer L, Feldner A, Hecker M, Korff T (2012) Hypertension impairs myocardin function: a novel mechanism facilitating arterial remodelling. Cardiovasc Res 96:120–129

    Article  CAS  PubMed  Google Scholar 

  61. Li C, Wernig F, Leitges M, Hu Y, Xu Q (2003) Mechanical stress-activated PKCdelta regulates smooth muscle cell migration. FASEB J 17:2106–2108

    Article  CAS  PubMed  Google Scholar 

  62. Gawlak G, Son S, Tian Y, O’Donnell JJ 3rd, Birukov KG, Birukova AA (2016) Chronic high-magnitude cyclic stretch stimulates EC inflammatory response via VEGF receptor 2-dependent mechanism. Am J Physiol Lung Cell Mol Physiol 310:L1062–L1070

    Article  PubMed  PubMed Central  Google Scholar 

  63. Esteller M (2002) CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future. Oncogene 21:5427–5440

    Article  CAS  PubMed  Google Scholar 

  64. Portela A, Esteller M (2010) Epigenetic modifications and human disease. Nat Biotechnol 28:1057–1068

    Article  CAS  PubMed  Google Scholar 

  65. Deplus R, Brenner C, Burgers WA, Putmans P, Kouzarides T, de Launoit Y, Fuks F (2002) Dnmt3L is a transcriptional repressor that recruits histone deacetylase. Nucleic Acids Res 30:3831–3838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Esteller M, Herman JG (2002) Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J Pathol 196:1–7

    Article  CAS  PubMed  Google Scholar 

  67. Weinhold B (2006) Epigenetics: the science of change. Environ Health Perspect 114:A160–A167

    Article  PubMed  PubMed Central  Google Scholar 

  68. Reik W, Dean W, Walter J (2001) Epigenetic reprogramming in mammalian development. Science 293:1089–1093

    Article  CAS  PubMed  Google Scholar 

  69. Rao X, Zhong J, Zhang S, Zhang Y, Yu Q, Yang P, Wang MH, Fulton DJ, Shi H, Dong Z et al (2011) Loss of methyl-CpG-binding domain protein 2 enhances endothelial angiogenesis and protects mice against hind-limb ischemic injury. Circulation 123:2964–2974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Greissel A, Culmes M, Napieralski R, Wagner E, Gebhard H, Schmitt M, Zimmermann A, Eckstein HH, Zernecke A, Pelisek J (2015) Alternation of histone and DNA methylation in human atherosclerotic carotid plaques. Thromb Haemost 114:390–402

    Article  CAS  PubMed  Google Scholar 

  71. Wierda RJ, Rietveld IM, van Eggermond MC, Belien JA, van Zwet EW, Lindeman JH, van den Elsen PJ (2015) Global histone H3 lysine 27 triple methylation levels are reduced in vessels with advanced atherosclerotic plaques. Life Sci 129:3–9

    Article  CAS  PubMed  Google Scholar 

  72. Liu Y, Peng W, Qu K, Lin X, Zeng Z, Chen J, Wei D, Wang Z (2018) TET2: a novel epigenetic regulator and potential intervention target for atherosclerosis. DNA Cell Biol 37:517–523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ (1997) Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389:251–260

    Article  CAS  PubMed  Google Scholar 

  74. Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705

    Article  CAS  PubMed  Google Scholar 

  75. Sterner DE, Berger SL (2000) Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev 64:435–459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Haberland M, Montgomery RL, Olson EN (2009) The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 10:32–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Witt O, Deubzer HE, Milde T, Oehme I (2009) HDAC family: what are the cancer relevant targets? Cancer Lett 277:8–21

    Article  CAS  PubMed  Google Scholar 

  78. Delcuve GP, Khan DH, Davie JR (2012) Roles of histone deacetylases in epigenetic regulation: emerging paradigms from studies with inhibitors. Clin Epigenetics 4:5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Wang GG, Allis CD, Chi P (2007) Chromatin remodeling and cancer, Part I: Covalent histone modifications. Trends Mol Med 13:363–372

    Article  CAS  PubMed  Google Scholar 

  80. Haigis MC, Guarente LP (2006) Mammalian sirtuins–emerging roles in physiology, aging, and calorie restriction. Genes Dev 20:2913–2921

    Article  CAS  PubMed  Google Scholar 

  81. Wade PA (2001) Transcriptional control at regulatory checkpoints by histone deacetylases: molecular connections between cancer and chromatin. Hum Mol Genet 10:693–698

    Article  CAS  PubMed  Google Scholar 

  82. Wang Y, Miao X, Liu Y, Li F, Liu Q, Sun J, Cai L (2014) Dysregulation of histone acetyltransferases and deacetylases in cardiovascular diseases. Oxid Med Cell Longev 2014:641979

    Article  PubMed  PubMed Central  Google Scholar 

  83. Bolden JE, Peart MJ, Johnstone RW (2006) Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 5:769–784

    Article  CAS  PubMed  Google Scholar 

  84. Xu WS, Parmigiani RB, Marks PA (2007) Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene 26:5541–5552

    Article  CAS  PubMed  Google Scholar 

  85. Kim HJ, Bae SC (2011) Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs. Am J Transl Res 3:166–179

    CAS  PubMed  Google Scholar 

  86. Holoch D, Moazed D (2015) RNA-mediated epigenetic regulation of gene expression. Nat Rev Genet 16:71–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Stefani G, Slack FJ (2008) Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol 9:219–230

    Article  CAS  PubMed  Google Scholar 

  88. Mattick JS (2009) The genetic signatures of noncoding RNAs. PLoS Genet 5:e1000459

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Holoch D, Moazed D (2015) Small-RNA loading licenses Argonaute for assembly into a transcriptional silencing complex. Nat Struct Mol Biol 22:328–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Erwin JA, Lee JT (2008) New twists in X-chromosome inactivation. Curr Opin Cell Biol 20:349–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Small EM, Olson EN (2011) Pervasive roles of microRNAs in cardiovascular biology. Nature 469:336–342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Weber C, Schober A, Zernecke A (2010) MicroRNAs in arterial remodelling, inflammation and atherosclerosis. Curr Drug Targets 11:950–956

    Article  CAS  PubMed  Google Scholar 

  93. Chen LJ, Chuang L, Huang YH, Zhou J, Lim SH, Lee CI, Lin WW, Lin TE, Wang WL, Chen L, Chien S, Chiu JJ (2015) MicroRNA mediation of endothelial inflammatory response to smooth muscle cells and its inhibition by atheroprotective shear stress. Circ Res 116:1157–1169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. 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 15:272–284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. 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 U S A 105:1516–1521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. 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 460:705–710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Holdt LM, Beutner F, Scholz M, Gielen S, Gabel G, Bergert H, Schuler G, Thiery J, Teupser D (2010) ANRIL expression is associated with atherosclerosis risk at chromosome 9p21. Arterioscler Thromb Vasc Biol 30:620–627

    Article  CAS  PubMed  Google Scholar 

  98. Zhou X, Han X, Wittfeldt A, Sun J, Liu C, Wang X, Gan LM, Cao H, Liang Z (2016) Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-kappaB pathway. RNA Biol 13:98–108

    Article  PubMed  Google Scholar 

  99. Congrains A, Kamide K, Ohishi M, Rakugi H (2013) ANRIL: molecular mechanisms and implications in human health. Int J Mol Sci 14:1278–1292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Wu G, Cai J, Han Y, Chen J, Huang ZP, Chen C, Cai Y, Huang H, Yang Y, Liu Y et al (2014) LincRNA-p21 regulates neointima formation, vascular smooth muscle cell proliferation, apoptosis, and atherosclerosis by enhancing p53 activity. Circulation 130:1452–1465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Michalik KM, You X, Manavski Y, Doddaballapur A, Zornig M, Braun T, John D, Ponomareva Y, Chen W, Uchida S et al (2014) Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res 114:1389–1397

    Article  CAS  PubMed  Google Scholar 

  102. Cremer S, Michalik KM, Fischer A, Pfisterer L, Jae N, Winter C, Boon RA, Muhly-Reinholz M, John D, Uchida S et al (2019) Hematopoietic deficiency of the long noncoding RNA MALAT1 promotes atherosclerosis and plaque inflammation. Circulation 139:1320–1334

    Article  CAS  PubMed  Google Scholar 

  103. Dunn J, Qiu H, Kim S, Jjingo D, Hoffman R, Kim CW, Jang I, Son DJ, Kim D, Pan C et al (2014) Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosis. J Clin Invest 124:3187–3199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Zhang YP, Huang YT, Huang TS, Pang W, Zhu JJ, Liu YF, Tang RZ, Zhao CR, Yao WJ, Li YS et al (2017) The mammalian target of rapamycin and DNA methyltransferase 1 axis mediates vascular endothelial dysfunction in response to disturbed flow. Sci Rep 7:14996

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Jiang YZ, Jimenez JM, Ou K, McCormick ME, Zhang LD, Davies PF (2014) Hemodynamic disturbed flow induces differential DNA methylation of endothelial Kruppel-Like Factor 4 promoter in vitro and in vivo. Circ Res 115:32–43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Yang Q, Li X, Li R, Peng J, Wang Z, Jiang Z, Tang X, Peng Z, Wang Y, Wei D (2016) Low shear stress inhibited endothelial cell autophagy through TET2 downregulation. Ann Biomed Eng 44:2218–2227

    Article  PubMed  Google Scholar 

  107. Zeng L, Zhang Y, Chien S, Liu X, Shyy JY (2003) The role of p53 deacetylation in p21Waf1 regulation by laminar flow. J Biol Chem 278:24594–24599

    Article  CAS  PubMed  Google Scholar 

  108. Lee DY, Lee CI, Lin TE, Lim SH, Zhou J, Tseng YC, Chien S, Chiu JJ (2012) Role of histone deacetylases in transcription factor regulation and cell cycle modulation in endothelial cells in response to disturbed flow. Proc Natl Acad Sci U S A 109:1967–1972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Zampetaki A, Zeng L, Margariti A, Xiao Q, Li H, Zhang Z, Pepe AE, Wang G, Habi O, deFalco E et al (2010) Histone deacetylase 3 is critical in endothelial survival and atherosclerosis development in response to disturbed flow. Circulation 121:132–142

    Article  CAS  PubMed  Google Scholar 

  110. Yan ZQ, Yao QP, Zhang ML, Qi YX, Guo ZY, Shen BR, Jiang ZL (2009) Histone deacetylases modulate vascular smooth muscle cell migration induced by cyclic mechanical strain. J Biomech 42:945–948

    Article  PubMed  Google Scholar 

  111. Usui T, Okada M, Hara Y, Yamawaki H (2011) Exploring calmodulin-related proteins, which mediate development of hypertension, in vascular tissues of spontaneous hypertensive rats. Biochem Biophys Res Commun 405:47–51

    Article  CAS  PubMed  Google Scholar 

  112. Wang W, Ha CH, Jhun BS, Wong C, Jain MK, Jin ZG (2010) Fluid shear stress stimulates phosphorylation-dependent nuclear export of HDAC5 and mediates expression of KLF2 and eNOS. Blood 115:2971–2979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Wang YH, Yan ZQ, Qi YX, Cheng BB, Wang XD, Zhao D, Shen BR, Jiang ZL (2010) Normal shear stress and vascular smooth muscle cells modulate migration of endothelial cells through histone deacetylase 6 activation and tubulin acetylation. Ann Biomed Eng 38:729–737

    Article  PubMed  Google Scholar 

  114. Chen Z, Peng IC, Cui X, Li YS, Chien S, Shyy JY (2010) Shear stress, SIRT1, and vascular homeostasis. Proc Natl Acad Sci U S A 107:10268–10273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Chen W, Bacanamwo M, Harrison DG (2008) Activation of p300 histone acetyltransferase activity is an early endothelial response to laminar shear stress and is essential for stimulation of endothelial nitric-oxide synthase mRNA transcription. J Biol Chem 283:16293–16298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Nicoli S, Standley C, Walker P, Hurlstone A, Fogarty KE, Lawson ND (2010) MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. Nature 464:1196–1200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. 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:H1762–H1769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Zhou J, Wang KC, Wu W, Subramaniam S, Shyy JY, Chiu JJ, Li JY, Chien S (2011) MicroRNA-21 targets peroxisome proliferators-activated receptor-alpha in an autoregulatory loop to modulate flow-induced endothelial inflammation. Proc Natl Acad Sci U S A 108:10355–10360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. 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 U S A 107:13450–13455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Lee DY, Lin TE, Lee CI, Zhou J, Huang YH, Lee PL, Shih YT, Chien S, Chiu JJ (2017) MicroRNA-10a is crucial for endothelial response to different flow patterns via interaction of retinoid acid receptors and histone deacetylases. Proc Natl Acad Sci U S A 114:2072–2077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Lee DY, Yang TL, Huang YH, Lee CI, Chen LJ, Shih YT, Wei SY, Wang WL, Wu CC, Chiu JJ (2018) Induction of microRNA-10a using retinoic acid receptor-alpha and retinoid x receptor-alpha agonists inhibits atherosclerotic lesion formation. Atherosclerosis 271:36–44

    Article  CAS  PubMed  Google Scholar 

  122. Wu W, Xiao H, Laguna-Fernandez A, Villarreal G Jr, Wang KC, Geary GG, Zhang Y, Wang WC, Huang HD, Zhou J et al (2011) Flow-dependent regulation of Kruppel-like factor 2 is mediated by microRNA-92a. Circulation 124:633–641

    Article  CAS  PubMed  Google Scholar 

  123. 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 U S A 107:3240–3244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Wang KC, Garmire LX, Young A, Nguyen P, Trinh A, Subramaniam S, Wang N, Shyy JY, Li YS, Chien S (2010) Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth. Proc Natl Acad Sci U S A 107:3234–3239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. 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 427:138–142

    Article  CAS  PubMed  Google Scholar 

  126. Mohamed JS, Lopez MA, Boriek AM (2010) Mechanical stretch up-regulates microRNA-26a and induces human airway smooth muscle hypertrophy by suppressing glycogen synthase kinase-3beta. J Biol Chem 285:29336–29347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. 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 24:1087–1093

    Article  CAS  PubMed  Google Scholar 

  128. Yu ML, Wang JF, Wang GK, You XH, Zhao XX, Jing Q, Qin YW (2011) Vascular smooth muscle cell proliferation is influenced by let-7d microRNA and its interaction with KRAS. Circ J 75:703–709

    Article  CAS  PubMed  Google Scholar 

  129. Huang K, Bao H, Yan ZQ, Wang L, Zhang P, Yao QP, Shi Q, Chen XH, Wang KX, Shen BR et al (2017) MicroRNA-33 protects against neointimal hyperplasia induced by arterial mechanical stretch in the grafted vein. Cardiovasc Res 113:488–497

    CAS  PubMed  Google Scholar 

  130. Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets AJ, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M et al (2012) Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol 14:249–256

    Article  CAS  PubMed  Google Scholar 

  131. Zhu JJ, Liu YF, Zhang YP, Zhao CR, Yao WJ, Li YS, Wang KC, Huang TS, Pang W, Wang XF et al (2017) VAMP3 and SNAP23 mediate the disturbed flow-induced endothelial microRNA secretion and smooth muscle hyperplasia. Proc Natl Acad Sci U S A 114:8271–8276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Leisegang MS, Bibli SI, Gunther S, Pfluger-Muller B, Oo JA, Hoper C, Seredinski S, Yekelchyk M, Schmitz-Rixen T, Schurmann C et al (2019) Pleiotropic effects of laminar flow and statins depend on the Kruppel-like factor-induced lncRNA MANTIS. Eur Heart J 40:2523–2533

    Article  CAS  PubMed  Google Scholar 

  133. Lund G, Andersson L, Lauria M, Lindholm M, Fraga MF, Villar-Garea A, Ballestar E, Esteller M, Zaina S (2004) DNA methylation polymorphisms precede any histological sign of atherosclerosis in mice lacking apolipoprotein E. J Biol Chem 279:29147–29154

    Article  CAS  PubMed  Google Scholar 

  134. Hiltunen MO, Turunen MP, Hakkinen TP, Rutanen J, Hedman M, Makinen K, Turunen AM, Aalto-Setala K, Yla-Herttuala S (2002) DNA hypomethylation and methyltransferase expression in atherosclerotic lesions. Vasc Med 7:5–11

    Article  PubMed  Google Scholar 

  135. Zhong W, Li B, Xu Y, Yang P, Chen R, Wang Z, Shao C, Song J, Yan J (2018) Hypermethylation of the micro-RNA 145 promoter is the key regulator for NLRP3 inflammasome-induced activation and plaque formation. JACC Basic Transl Sci 3:604–624

    Article  PubMed  PubMed Central  Google Scholar 

  136. Tai SC, Robb GB, Marsden PA (2004) Endothelial nitric oxide synthase: a new paradigm for gene regulation in the injured blood vessel. Arterioscler Thromb Vasc Biol 24:405–412

    Article  CAS  PubMed  Google Scholar 

  137. Cardinale JP, Sriramula S, Pariaut R, Guggilam A, Mariappan N, Elks CM, Francis J (2010) HDAC inhibition attenuates inflammatory, hypertrophic, and hypertensive responses in spontaneously hypertensive rats. Hypertension 56:437–444

    Article  CAS  PubMed  Google Scholar 

  138. Stein S, Matter CM (2011) Protective roles of SIRT1 in atherosclerosis. Cell Cycle 10:640–647

    Article  CAS  PubMed  Google Scholar 

  139. Balligand JL, Feron O, Dessy C (2009) eNOS activation by physical forces: from short-term regulation of contraction to chronic remodeling of cardiovascular tissues. Physiol Rev 89:481–534

    Article  CAS  PubMed  Google Scholar 

  140. Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, Xiao T, Schafer J, Lee ML, Schmittgen TD et al (2008) Detection of microRNA expression in human peripheral blood microvesicles. PLoS One 3:e3694

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 105:10513–10518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, Mitchell PS, Bennett CF, Pogosova-Agadjanyan EL, Stirewalt DL et al (2011) Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A 108:5003–5008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Noferesti SS, Sohel MM, Hoelker M, Salilew-Wondim D, Tholen E, Looft C, Rings F, Neuhoff C, Schellander K, Tesfaye D (2015) Controlled ovarian hyperstimulation induced changes in the expression of circulatory miRNA in bovine follicular fluid and blood plasma. J Ovarian Res 8:81

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  144. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659

    Article  CAS  PubMed  Google Scholar 

  145. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997–1006

    Article  CAS  PubMed  Google Scholar 

  146. Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, Benjamin H, Kushnir M, Cholakh H, Melamed N et al (2008) Serum microRNAs are promising novel biomarkers. PLoS One 3:e3148

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  147. Sisco KL (2001) Is RNA in serum bound to nucleoprotein complexes? Clin Chem 47:1744–1745

    Article  CAS  PubMed  Google Scholar 

  148. El-Hefnawy T, Raja S, Kelly L, Bigbee WL, Kirkwood JM, Luketich JD, Godfrey TE (2004) Characterization of amplifiable, circulating RNA in plasma and its potential as a tool for cancer diagnostics. Clin Chem 50:564–573

    Article  CAS  PubMed  Google Scholar 

  149. Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan L, Denecke B, Hristov M, Koppel T, Jahantigh MN, Lutgens E et al (2009) Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal 2:ra81

    Article  PubMed  Google Scholar 

  150. Pfeifer P, Werner N, Jansen F (2015) Role and function of microRNAs in extracellular vesicles in cardiovascular biology. Biomed Res Int 2015:161393

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  151. Khyzha N, Alizada A, Wilson MD, Fish JE (2017) Epigenetics of atherosclerosis: emerging mechanisms and methods. Trends Mol Med 23:332–347

    Article  CAS  PubMed  Google Scholar 

  152. Arslan S, Berkan O, Lalem T, Ozbilum N, Goksel S, Korkmaz O, Cetin N, Devaux Y, Cardiolinc n (2017) Long non-coding RNAs in the atherosclerotic plaque. Atherosclerosis 266:176–181

    Article  CAS  PubMed  Google Scholar 

  153. Man HSJ, Sukumar AN, Lam GC, Turgeon PJ, Yan MS, Ku KH, Dubinsky MK, Ho JJD, Wang JJ, Das S et al (2018) Angiogenic patterning by STEEL, an endothelial-enriched long noncoding RNA. Proc Natl Acad Sci U S A 115:2401–2406

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  154. Josipovic I, Pfluger B, Fork C, Vasconez AE, Oo JA, Hitzel J, Seredinski S, Gamen E, Heringdorf DMZ, Chen W et al (2018) Long noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function. J Mol Cell Cardiol 116:57–68

    Article  CAS  PubMed  Google Scholar 

  155. Raines EW (2000) The extracellular matrix can regulate vascular cell migration, proliferation, and survival: relationships to vascular disease. Int J Exp Pathol 81:173–182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by the Taiwan Ministry of Science and Technology grants MOST-108-2321-B-400-001 and 106-2320-B-400-030-MY3.

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Authors and Affiliations

  1. Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan

    Shu-Yi Wei & Jeng-Jiann Chiu

  2. School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

    Jeng-Jiann Chiu

  3. College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

    Jeng-Jiann Chiu

  4. Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan

    Jeng-Jiann Chiu

  5. Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan

    Jeng-Jiann Chiu

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  1. Shu-Yi Wei
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Correspondence to Jeng-Jiann Chiu .

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  1. Department of Cardiovascular Physiology, Heidelberg University, Heidelberg, Germany

    Markus Hecker

  2. Experimental Cardiology Department of Cardiology, Thorax Center, Erasmus University Medical Center, Rotterdam, The Netherlands

    Dirk J. Duncker

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Wei, SY., Chiu, JJ. (2021). Mechanical Regulation of Epigenetic Modifications in Vascular Biology and Pathobiology. In: Hecker, M., Duncker, D.J. (eds) Vascular Mechanobiology in Physiology and Disease. Cardiac and Vascular Biology, vol 8. Springer, Cham. https://doi.org/10.1007/978-3-030-63164-2_9

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