Endothelial Epigenetics in Biomechanical Stress: Disturbed Flow-Mediated Epigenomic Plasticity in Vivo and in Vitro

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 35, Issue 6, 2015, Pages 1317-1326

  Jiang, Yi Zhou ^a   Manduchi, Elisabetta ^a   Jiménez, Juan M ^a   Davies, Peter F ^a,b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

atherogenesis; chromatin assembly and disassembly; DNA methylation; epigenomics; hemodynamics

Indexed keywords

DNA METHYLTRANSFERASE; DNA METHYLTRANSFERASE 1; DNA METHYLTRANSFERASE 3A; HISTONE; HISTONE DEACETYLASE; KRUPPEL LIKE FACTOR 4; LONG UNTRANSLATED RNA; MICRORNA; UNTRANSLATED RNA; DMAP1 PROTEIN, HUMAN; DNA (CYTOSINE 5) METHYLTRANSFERASE; REPRESSOR PROTEIN;

ARTICLE; ATHEROGENESIS; BLOOD FLOW; CHROMATIN ASSEMBLY AND DISASSEMBLY; CONFORMATION; DNA METHYLATION; ENDOTHELIAL DYSFUNCTION; EPIGENETICS; GENE EXPRESSION; GENETIC SUSCEPTIBILITY; HEMODYNAMICS; HISTONE MODIFICATION; HOMEOBOX; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MECHANICAL STRESS; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; SHEAR STRESS; TRANSCRIPTION REGULATION; TRANSLATION REGULATION; VASCULAR ENDOTHELIUM; ANIMAL; ATHEROSCLEROSIS; GENETIC EPIGENESIS; GENETIC TRANSCRIPTION; GENETICS; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; TRANSLATIONAL PROTEIN MODIFICATION;

ANIMALS; ATHEROSCLEROSIS; DNA (CYTOSINE-5-)-METHYLTRANSFERASE; DNA METHYLATION; ENDOTHELIUM, VASCULAR; EPIGENESIS, GENETIC; GENES, HOMEOBOX; HEMODYNAMICS; HISTONES; MICRORNAS; PHENOTYPE; PROTEIN MODIFICATION, TRANSLATIONAL; REPRESSOR PROTEINS; RNA, LONG NONCODING; STRESS, MECHANICAL; TRANSCRIPTION, GENETIC;

EID: 84933047057     PISSN: 10795642     EISSN: 15244636     Source Type: Journal    
DOI: 10.1161/ATVBAHA.115.303427     Document Type: Article

References (70)

1. Davies PF. Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology. Nat Clin Pract Cardiovasc Med. 2009;6:16-26. doi: 10.1038/ncpcardio1397.
2. Chiu JJ, Chien S. Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol Rev. 2011;91:327-387. doi: 10.1152/physrev.00047.2009.
3. Hajra L, Evans AI, Chen M, Hyduk SJ, Collins T, Cybulsky MI. The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc Natl Acad Sci USA. 2000;97:9052-9057.
4. Passerini AG, Polacek DC, Shi C, Francesco NM, Manduchi E, Grant GR, Pritchard WF, Powell S, Chang GY, Stoeckert CJ Jr, Davies PF. Coexisting proinflammatory and antioxidative endothelial transcription profiles in a disturbed flow region of the adult porcine aorta. Proc Natl Acad Sci USA. 2004;101:2482-2487.
5. Davies PF. Flow-mediated endothelial mechanotransduction. Physiol Rev. 1995;75:519-560.
6. Dull RO, Tarbell JM, Davies PF. Mechanisms of flow-mediated signal transduction in endothelial cells: kinetics of ATP surface concentrations. J Vasc Res. 1992;29:410-419.
7. Jones CI 3rd, Han Z, Presley T, Varadharaj S, Zweier JL, Ilangovan G, Alevriadou BR. Endothelial cell respiration is affected by the oxygen tension during shear exposure: role of mitochondrial peroxynitrite. Am J Physiol Cell Physiol. 2008;295:C180-C191. doi: 10.1152/ajpcell.00549.2007.
8. Zhou J, Li YS, Chien S. Shear stress-initiated signaling and its regulation of endothelial function. Arterioscler Thromb Vasc Biol. 2014;34:2191-2198. doi: 10.1161/ATVBAHA.114.303422.
9. Bryan MT, Duckles H, Feng S, Hsiao ST, Kim HR, Serbanovic-Canic J, Evans PC. Mechanoresponsive networks controlling vascular inflammation. Arterioscler Thromb Vasc Biol. 2014;34:2199-2205. doi: 10.1161/ATVBAHA.114.303424.
10. Kumar S, Kim CW, Simmons RD, Jo H. Role of flow-sensitive microRNAs in endothelial dysfunction and atherosclerosis: mechanosensitive athero-miRs. Arterioscler Thromb Vasc Biol. 2014;34:2206-2216. doi: 10.1161/ATVBAHA.114.303425.
11. Mau T, Yung R. Potential of epigenetic therapies in non-cancerous conditions. Front Genet. 2014;5:438. doi: 10.3389/fgene.2014.00438.
12. Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003;33 Suppl:245-254. doi: 10.1038/ng1089.
13. Maunakea AK, Chepelev I, Zhao K. Epigenome mapping in normal and disease States. Circ Res. 2010;107:327-339. doi: 10.1161/CIRCRESAHA.110.222463.
14. Webster AL, Yan MS, Marsden PA. Epigenetics and cardiovascular disease. Can J Cardiol. 2013;29:46-57. doi: 10.1016/j.cjca.2012.10.023.
15. Lee JT. Epigenetic regulation by long noncoding RNAs. Science. 2012;338:1435-1439. doi: 10.1126/science.1231776.
16. Turgeon PJ, Sukumar AN, Marsden PA. Epigenetics of cardiovascular disease-a new beat in coronary artery disease. Med Epigenet. 2014;2:37-52. doi: 10.1159/000360766.
17. Matouk CC, Marsden PA. Epigenetic regulation of vascular endothelial gene expression. Circ Res. 2008;102:873-887. doi: 10.1161/CIRCRESAHA.107.171025.
18. Severin PM, Zou X, Gaub HE, Schulten K. Cytosine methylation alters DNA mechanical properties. Nucleic Acids Res. 2011;39:8740-8751. doi: 10.1093/nar/gkr578.
19. Weber M, Davies JJ, Wittig D, Oakeley EJ, Haase M, Lam WL, Schübeler D. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet. 2005;37:853-862. doi: 10.1038/ng1598.
20. Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature. 1998;393:386-389. doi: 10.1038/30764.
21. Denis H, Ndlovu MN, Fuks F. Regulation of mammalian DNA methyltransferases: a route to new mechanisms. EMBO Rep. 2011;12:647-656. doi: 10.1038/embor.2011.110.
22. O'Hagan HM, Wang W, Sen S, Destefano Shields C, Lee SS, Zhang YW, Clements EG, Cai Y, Van Neste L, Easwaran H, Casero RA, Sears CL, Baylin SB. Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG Islands. Cancer Cell. 2011;20:606-619. doi: 10.1016/j.ccr.2011.09.012.
23. Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012;13:484-492. doi: 10.1038/nrg3230.
24. Bhutani N, Burns DM, Blau HM. DNA demethylation dynamics. Cell. 2011;146:866-872. doi: 10.1016/j.cell.2011.08.042.
25. Jia D, Jurkowska RZ, Zhang X, Jeltsch A, Cheng X. Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature. 2007;449:248-251. doi: 10.1038/nature06146.
26. Kornberg RD, Lorch Y. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell. 1999;98:285-294.
27. Bannister AJ, Kouzarides T. Histone methylation: recognizing the methyl mark. Methods Enzymol. 2004;376:269-288. doi: 10.1016/S0076-6879(03)76018-2.
28. Ambros V. The functions of animal microRNAs. Nature. 2004;431:350-355. doi: 10.1038/nature02871.
29. Fang Y, Shi C, Manduchi E, Civelek M, Davies PF. MicroRNA-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitro. Proc Natl Acad Sci USA. 2010;107:13450-13455. doi: 10.1073/pnas.1002120107.
30. Fang Y, Davies PF. Site-specific microRNA-92a regulation of Kruppellike factors 4 and 2 in atherosusceptible endothelium. Arterioscler Thromb Vasc Biol. 2012;32:979-987. doi: 10.1161/ATVBAHA.111.244053.
31. Zhou J, Lim SH, Chiu J-J. Epigenetic regulation of vascular endothelial biology/pathobiology and response to fluid shear stress. Cell Mol Bioengineering. 2011;4:560-578.
32. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215-233. doi: 10.1016/j.cell.2009.01.002.
33. Liang M. MicroRNA: a new entrance to the broad paradigm of systems molecular medicine. Physiol Genomics. 2009;38:113-115. doi: 10.1152/physiolgenomics.00080.2009.
34. Chuang JC, Jones PA. Epigenetics and microRNAs. Pediatr Res. 2007;61(5 Pt 2):24R-29R. doi: 10.1203/pdr.0b013e3180457684.
35. Rajewsky N. microRNA target predictions in animals. Nat Genet. 2006;38 Suppl:S8-13. doi: 10.1038/ng1798.
36. Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA, Jones PA. Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell. 2006;9:435-443. doi: 10.1016/j.ccr.2006.04.020.
37. Hartung CT, Michalik KM, You X, Chen W, Zeiher AM, Boon RA, Dimmeler S. Regulation and function of the laminar flow-induced non-coding RNAs in endothelial cells. Circulation. 2014:130:A18783 (Abstract)
38. Choi JH, Nam KH, Kim J, Baek MW, Park JE, Park HY, Kwon HJ, Kwon OS, Kim DY, Oh GT. Trichostatin A exacerbates atherosclerosis in low density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2005;25:2404-2409. doi: 10.1161/01.ATV.0000184758.07257.88.
39. Laukkanen MO, Kivelä A, Rissanen T, Rutanen J, Karkkainen MK, Leppanen O, Bräsen JH, Yla-Herttuala S. Adenovirus-mediated extracellular superoxide dismutase gene therapy reduces neointima formation in balloon-denuded rabbit aorta. Circulation. 2002;106:1999-2003.
40. Hiltunen MO, Ylä-Herttuala S. DNA methylation, smooth muscle cells, and atherogenesis. Arterioscler Thromb Vasc Biol. 2003;23:1750-1753. doi: 10.1161/01.ATV.0000092871.30563.41.
41. Lund G, Andersson L, Lauria M, Lindholm M, Fraga MF, Villar-Garea A, Ballestar E, Esteller M, Zaina S. DNA methylation polymorphisms precede any histological sign of atherosclerosis in mice lacking apolipoprotein E. J Biol Chem. 2004;279:29147-29154. doi: 10.1074/jbc.M403618200.
42. Dunn J, Qiu H, Kim S, Jjingo D, Hoffman R, Kim CW, Jang I, Son DJ, Kim D, Pan C, Fan Y, Jordan IK, Jo H. Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosis. J Clin Invest. 2014;124:3187-3199. doi: 10.1172/JCI74792.
43. Civelek M, Manduchi E, Riley RJ, Stoeckert CJ Jr, Davies PF. Chronic endoplasmic reticulum stress activates unfolded protein response in arterial endothelium in regions of susceptibility to atherosclerosis. Circ Res. 2009;105:453-461. doi: 10.1161/CIRCRESAHA.109.203711.
44. Davies PF, Civelek M. Endoplasmic reticulum stress, redox, and a proinflammatory environment in athero-susceptible endothelium in vivo at sites of complex hemodynamic shear stress. Antioxid Redox Signal. 2011;15:1427-1432. doi: 10.1089/ars.2010.3741.
45. Zhou J, Li YS, Wang KC, Chien S. Epigenetic Mechanism in Regulation of Endothelial Function by Disturbed Flow: Induction of DNA Hypermethylation by DNMT1. Cell Mol Bioeng. 2014;7:218-224. doi: 10.1007/s12195-014-0325-z.
46. Pearson JC, Lemons D, McGinnis W. Modulating Hox gene functions during animal body patterning. Nat Rev Genet. 2005;6:893-904. doi: 10.1038/nrg1726.
47. Pruett ND, Visconti RP, Jacobs DF, Scholz D, McQuinn T, Sundberg JP, Awgulewitsch A. Evidence for Hox-specified positional identities in adult vasculature. BMC Dev Biol. 2008;8:93. doi: 10.1186/1471-213X-8-93.
48. Douville JM, Wigle JT. Regulation and function of homeodomain proteins in the embryonic and adult vascular systems. Can J Physiol Pharmacol. 2007;85:55-65. doi: 10.1139/y06-091.
49. Jiang YZ, Jiménez JM, Ou K, McCormick ME, Zhang LD, Davies PF. Hemodynamic disturbed flow induces differential DNA methylation of endothelial Kruppel-Like Factor 4 promoter in vitro and in vivo. Circ Res. 2014;115:32-43. doi: 10.1161/CIRCRESAHA.115.303883.
50. Ling Y, Sankpal UT, Robertson AK, McNally JG, Karpova T, Robertson KD. Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription. Nucleic Acids Res. 2004;32:598-610. doi: 10.1093/nar/gkh195.
51. Villarreal G Jr, Zhang Y, Larman HB, Gracia-Sancho J, Koo A, García-Cardeña G. Defining the regulation of KLF4 expression and its downstream transcriptional targets in vascular endothelial cells. Biochem Biophys Res Commun. 2010;391:984-989. doi: 10.1016/j.bbrc.2009.12.002.
52. Hamik A, Lin Z, Kumar A, Balcells M, Sinha S, Katz J, Feinberg MW, Gerzsten RE, Edelman ER, Jain MK. Kruppel-like factor 4 regulates endothelial inflammation. J Biol Chem. 2007;282:13769-13779. doi: 10.1074/jbc.M700078200.
53. Zhou G, Hamik A, Nayak L, et al. Endothelial Kruppel-like factor 4 protects against atherothrombosis in mice. J Clin Invest. 2012;122:4727-4731. doi: 10.1172/JCI66056.
54. Chan Y, Fish JE, D'Abreo C, Lin S, Robb GB, Teichert AM, Karantzoulis-Fegaras F, Keightley A, Steer BM, Marsden PA. The cell-specific expression of endothelial nitric-oxide synthase: a role for DNA methylation. J Biol Chem. 2004;279:35087-35100. doi: 10.1074/jbc.M405063200.
55. Shirodkar AV, St Bernard R, Gavryushova A, Kop A, Knight BJ, Yan MS, Man HS, Sud M, Hebbel RP, Oettgen P, Aird WC, Marsden PA. A mechanistic role for DNA methylation in endothelial cell (EC)-enriched gene expression: relationship with DNA replication timing. Blood. 2013;121:3531-3540. doi: 10.1182/blood-2013-01-479170.
56. Illi B, Nanni S, Scopece A, Farsetti A, Biglioli P, Capogrossi MC, Gaetano C. Shear stress-mediated chromatin remodeling provides molecular basis for flow-dependent regulation of gene expression. Circ Res. 2003;93:155-161. doi: 10.1161/01.RES.0000080933.82105.29.
57. Zeng L, Zhang Y, Chien S, Liu X, Shyy JY. The role of p53 deacetylation in p21Waf1 regulation by laminar flow. J Biol Chem. 2003;278:24594-24599. doi: 10.1074/jbc.M301955200.
58. Chen W, Bacanamwo M, Harrison DG. Activation of p300 histone acetyltransferase activity is an early endothelial response to laminar shear stress and is essential for stimulation of eNOS mRNA transcription. J Biol Chem. 2008;283:16293-16298.
59. Zampetaki A, Zeng L, Margariti A, Xiao Q, Li H, Zhang Z, Pepe AE, Wang G, Habi O, deFalco E, Cockerill G, Mason JC, Hu Y, Xu Q. Histone deacetylase 3 is critical in endothelial survival and atherosclerosis development in response to disturbed flow. Circulation. 2010;121:132-142. doi: 10.1161/CIRCULATIONAHA.109.890491.
60. Lee D-Y, Lee CI, Lin TE, Lim SH, Zhou J, Tseng Y-C, Chien S, Chiu J-J. Role of histone deacetylases in transcription factor regulation and cell cycle modulation in endothelial cells in response to disturbed flow.
61. Fledderus JO, Boon RA, Volger OL, Hurttila H, Ylä-Herttuala S, Pannekoek H, Levonen AL, Horrevoets AJ. KLF2 primes the antioxidant transcription factor Nrf2 for activation in endothelial cells. Arterioscler Thromb Vasc Biol. 2008;28:1339-1346. doi: 10.1161/ATVBAHA.108.165811.
62. Nioi P, McMahon M, Itoh K, Yamamoto M, Hayes JD. Identification of a novel Nrf2-regulated antioxidant response element (ARE) in the mouse NAD(P)H:quinone oxidoreductase 1 gene: reassessment of the ARE consensus sequence. Biochem J. 2003;374(Pt 2):337-348. doi: 10.1042/BJ20030754.
63. Motta MC, Divecha N, Lemieux M, Kamel C, Chen D, Gu W, Bultsma Y, McBurney M, Guarente L. Mammalian SIRT1 represses forkhead transcription factors. Cell. 2004;116:551-563.
64. Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavasky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004;303:2011-2015.
65. Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L, Gu W. Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell. 2001;107:137-148.
66. Chen Z, Peng I-C, Cui X, Li Y-S, Chien S, Shyy JY-J. Shear stress, SIRT1 and vascular homeostasis. Proc Natl Acad Sci USA. 2010;107:10268-10273.
67. Dekker RJ, van Soest S, Fontijn RD, Salamanca S, de Groot PG, VanBavel E, Pannekoek H, Horrevoets AJ. Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Kruppel-like factor (KLF2). Blood. 2002;100:1689-1698.
68. Markl M, Kilner PJ, Ebbers T. Comprehensive 4D velocity mapping of the heart and great vessels by cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2011;13:7. doi: 10.1186/1532-429X-13-7.
69. Davies PF, Manduchi E, Stoeckert CJ, Jimenez JM, Jiang Y-Z: Emerging topic: flow-related epigenetic regulation of the atherosusceptible endothelial phenotype through DNA methylation. Vascul Pharmacol. 2014;62:88-93.
70. Jiang Y-Z, Manduchi E, Stoeckert CJ, Davies PF. Arterial endothelial methylome: differential DNA methylation in athero-susceptible disturbed flow regions in vivo. BMC Genomics. 2015; in press.