Epigenetic Reprogramming in Atherosclerosis

Current Atherosclerosis Reports

Volumn 17, Issue 2, 2015, Pages

  Grimaldi, Vincenzo ^a   Vietri, Maria Teresa ^b   Schiano, Concetta ^c   Picascia, Antonietta ^a   De Pascale, Maria Rosaria ^a   Fiorito, Carmela ^a   Casamassimi, Amelia ^b   Napoli, Claudio ^a,c  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^b SECOND UNIVERSITY OF NAPLES   (Italy)

^c IRCCS SDN   (Italy)

Author keywords

Atherosclerosis; Endothelial dysfunction; Epigenetics; Hypercholesterolemia; Inflammation; Lipid metabolism

Indexed keywords

APOLIPOPROTEIN E; CHOLESTEROL; COLLAGEN; COLLAGEN TYPE 15 ALPHA1; ESTROGEN RECEPTOR; GAMMA INTERFERON; HOMOCYSTEINE; MEMBRANE PROTEIN; MESSENGER RNA; NITRIC OXIDE SYNTHASE; OXIDIZED LOW DENSITY LIPOPROTEIN RECEPTOR 1; PROTEIN P66SHC; TEN ELEVEN TRANSLOCATION PROTEIN; TRANSCRIPTION FACTOR FOXP3; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNTRANSLATED RNA; VASCULOTROPIN RECEPTOR; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; SMALL UNTRANSLATED RNA;

ATHEROGENESIS; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; CELL PROLIFERATION; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL SYNTHESIS; DISEASE ASSOCIATION; DNA METHYLATION; DNA MODIFICATION; ENDOTHELIAL DYSFUNCTION; EPIGENETICS; GENE EXPRESSION; HISTONE MODIFICATION; HUMAN; INFLAMMATION; LIPID METABOLISM; NONHUMAN; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; GENETIC EPIGENESIS; GENETICS; METABOLISM;

ATHEROSCLEROSIS; CHOLESTEROL; DNA METHYLATION; EPIGENESIS, GENETIC; HISTONE DEACETYLASE INHIBITORS; HISTONE DEACETYLASES; HUMANS; LIPID METABOLISM; RNA, SMALL UNTRANSLATED;

EID: 84937214006     PISSN: 15233804     EISSN: 15346242     Source Type: Journal    
DOI: 10.1007/s11883-014-0476-3     Document Type: Review

References (98)

1. Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473:317–25.
2. Schleithoff C, Voelter-Mahlknecht S, Dahmke IN, Mahlknecht U. On the epigenetics of vascular regulation and disease. Clin Epigenetics. 2012;4:7.
3. Barrès R, Osler ME, Yan J, et al. Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density. Cell Metab. 2009;10:189–98.
4. Udali S, Guarini P, Moruzzi S, et al. Cardiovascular epigenetics: from DNA methylation to microRNAs. Mol Asp Med. 2013;34:883–901.
5. Granger A, Abdullah I, Huebner F, et al. Histone deacetylase inhibition reduces myocardial ischemia-reperfusion injury in mice. FASEB J. 2008;22:3549–60.
6. Turunen MP, Aavik E, Ylä-Herttuala S. Epigenetics and atherosclerosis. Biochim Biophys Acta. 2009;1790:886–91.
7. Napoli C, Crudele V, Soricelli A, et al. Primary prevention of atherosclerosis: a clinical challenge for the reversal of epigenetic mechanisms? Circulation. 2012;125:2363–73. First relevant review on the topic of epigenetics and early human atherigenesis.
8. Kim GH, Ryan JJ, Archer SL. The role of redox signaling in epigenetics and cardiovascular disease. Antioxid Redox Signal. 2013;18:1920–36.
9. Paneni F, Costantino S, Volpe M, et al. Epigenetic signatures and vascular risk in type 2 diabetes: a clinical perspective. Atherosclerosis. 2013;230:191–7.
10. Krishna SM, Dear A, Craig JM, Norman PE, Golledge J. The potential role of homocysteine mediated DNA methylation and associated epigenetic changes in abdominal aortic aneurysm formation. Atherosclerosis. 2013;228:295–305.
11. Sato N, Maehara N, Su GH, Goggins M. Effects of 5-aza-2’-deoxycytidine on matrix metalloproteinase expression and pancreatic cancer cell invasiveness. J Natl Cancer Inst. 2003;19:327.
12. Borghini A, Cervelli T, Galli A, et al. DNA modifications in atherosclerosis: from the past to the future. Atherosclerosis. 2013;230:202–9.
13. Leung A, Trac C, Jin W, et al. Novel long noncoding RNAs are regulated by angiotensin II in vascular smooth muscle cells. Circ Res. 2013;113:266–78.
14. Lacolley P, Regnault V, Nicoletti A, Li Z, Michel JB. The vascular smooth muscle cell in arterial pathology: a cell that can take on multiple roles. Cardiovasc Res. 2012;95:194–204.
15. Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol. 2012;32:2045–51.
16. Pons D, de Vries FR, van den Elsen PJ, et al. Epigenetic histone acetylation modifiers in vascular remodelling: new targets for therapy in cardiovascular disease. Eur Heart J. 2009;30:266–77.
17. Napoli C, Paolisso G, Casamassimi A, et al. Effects of nitric oxide on cell proliferation: novel insights. J Am Coll Cardiol. 2013;62:89–95.
18. Yan MS, Matouk CC, Marsden PA. Epigenetics of the vascular endothelium. J Appl Physiol (1985). 2010;109:916–26.
19. Chan Y, Fish JE, D’Abreo C, et al. The cell-specific expression of endothelial nitric-oxide synthase: a role for DNA methylation. J Biol Chem. 2004;279:35087–100.
20. Breton CV, Park C, Siegmund K, et al. NOS1 methylation and carotid artery intima-media thickness in children. Circ Cardiovasc Genet. 2014;7:116–22.
21. Connelly JJ, Cherepanova OA, Doss JF, et al. Epigenetic regulation of COL15A1 in smooth muscle cell replicative aging and atherosclerosis. Hum Mol Genet. 2013;22:5107–20.
22. Zawadzki C, Chatelain N, Delestre M, et al. Tissue factor pathway inhibitor-2 gene methylation is associated with low expression in carotid atherosclerotic plaques. Atherosclerosis. 2009;204:4–14.
23. Liu R, Jin Y, Tang WH, et al. Ten-eleven translocation-2 (TET2) is a master regulator of smooth muscle cell plasticity. Circulation. 2013;128:2047–57. This study demonstrated evidence on the involvement of ten-eleven translocation-2 (TET2) in control of vascular smooth muscle cell (VSMC) plasticity and development of vascular disease.
24. Yamada Y, Nishida T, Horibe H, et al. Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation. Int J Mol Med. 2014;33:1355–63. An important genome-wide analysis of DNA methylation comparing atheromatous plaque lesions with corresponding plaque-free tissue that have confirmed the contribution of epigenetics to the pathogenesis of atherosclerosis.
25. Findeisen HM, Gizard F, Zhao Y, et al. Epigenetic regulation of vascular smooth muscle cell proliferation and neointima formation by histone deacetylase inhibition. Arterioscler Thromb Vasc Biol. 2011;31:851–60.
26. Xu Y. Transcriptional regulation of endothelial dysfunction in atherosclerosis: an epigenetic perspective. J Biomed Res. 2014;28:47–52.
27. Fish JE, Matouk CC, Rachlis A, et al. The expression of endothelial nitric-oxide synthase is controlled by a cell-specific histone code. J Biol Chem. 2005;280:24824–38.
28. Xiao Q, Zeng L, Zhang Z, et al. Sca-1+ progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury. Arterioscler Thromb Vasc Biol. 2006;26:2244–51.
29. Zampetaki A, Zeng L, Margariti A, et al. Histone deacetylase 3 is critical in endothelial survival and atherosclerosis development in response to disturbed flow. Circulation. 2010;121:132–42.
30. Hoeksema MA, Gijbels MJ, Van den Bossche J, et al. Targeting macrophage histone deacetylase 3 stabilizes atherosclerotic lesions. EMBO Mol Med. 2014;6:1124–32. Study that shown a link between histone modification and plaque vulnerability to rupture suggesting that epigenetic mechanisms could represent a potential novel therapeutic target in atherosclerosis.
31. Cao Q, Rong S, Repa JJ, et al. Histone deacetylase 9 represses cholesterol efflux and alternatively activated macrophages in atherosclerosis development. Arterioscler Thromb Vasc Biol. 2014;34:1871–9.
32. Zhou B, Margariti A, Zeng L, et al. Splicing of histone deacetylase 7 modulates smooth muscle cell proliferation and neointima formation through nuclear β-catenin translocation. Arterioscler Thromb Vasc Biol. 2011;31:2676–84.
33. Kavurma MM, Figg N, Bennett MR, et al. Oxidative stress regulates IGF1R expression in vascular smooth-muscle cells via p53 and HDAC recruitment. Biochem J. 2007;407:79–87.
34. Han S, Uludag MO, Usanmaz SE, et al. Resveratrol affects histone 3 lysine 27 methylation of vessels and blood biomarkers in DOCA salt-induced hypertension. Mol Biol Rep. 2014. doi:10.1007/s11033-014-3737-x.
35. Mathew OP, Ranganna K, Yatsu FM. Butyrate, an HDAC inhibitor, stimulates interplay between different posttranslational modifications of histone H3 and differently alters G1-specific cell cycle proteins in vascular smooth muscle cells. Biomed Pharmacother. 2010;64:733–40.
36. Pandey D, Sikka G, Bergman Y, et al. Transcriptional regulation of endothelial arginase 2 by histone deacetylase 2. Arterioscler Thromb Vasc Biol. 2014;34:1556–66.
37. Ji R, Cheng Y, Yue J, et al. MicroRNA expression signature and antisense-mediated depletion reveal an essential role of microRNA in vascular neointimal lesion formation. Circ Res. 2007;100:1579–88.
38. Wang M, Li W, Chang GQ, et al. MicroRNA-21 regulates vascular smooth muscle cell function via targeting tropomyosin 1 in arteriosclerosis obliterans of lower extremities. Arterioscler Thromb Vasc Biol. 2011;31:2044–53.
39. Li T, Cao H, Zhuang J, et al. Identification of miR-130a, miR-27b and miR-210 as serum biomarkers for atherosclerosis obliterans. Clin Chim Acta. 2011;412:66–70.
40. Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell. 2013;152:1298–307.
41. Holdt LM, Beutner F, Scholz M, et al. ANRIL expression is associated with atherosclerosis risk at chromosome 9p21. Arterioscler Thromb Vasc Biol. 2010;30:620–7.
42. Motterle A, Pu X, Wood H, et al. Functional analyses of coronary artery disease associated variation on chromosome 9p21 in vascular smooth muscle cells. Hum Mol Genet. 2012;21:4021–9.
43. Holdt LM, Hoffmann S, Sass K, et al. Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks. PLoS Genet. 2013;9:e1003588.
44. Papatheodorou L, Weiss N. Vascular oxidant stress and inflammation in hyperhomocysteinemia. Antioxid Redox Signa. 2007;9:1941–58.
45. Duell PB, Malinow MR. Homocysteine: an important risk factor for atherosclerotic vascular disease. Curr Opin Lipidol. 1997;8:28–34.
46. Handy DE, Castro R, Loscalzo J. Epigenetic modifications: basic mechanisms and role in cardiovascular disease. Circulation. 2011;123:2145–56.
47. Castro R, Rivera I, Struys EA, et al. Increased homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease. Clin Chem. 2003;49:1292.
48. Hiltunen MO, Turunen MP, Häkkinen TP, et al. DNA hypomethylation and methyltransferase expression in atherosclerotic lesions. Vasc Med. 2002;7:5–11.
49. Lund G, Andersson L, Lauria M, et al. DNA methylation polymorphisms precede any histological sign of atherosclerosis in mice lacking apolipoprotein E. J Biol Chem. 2004;279:29147–54.
50. Kim YR, Kim CS, Naqvi A, et al. Epigenetic upregulation of p66shc mediates low-density lipoprotein cholesterol-induced endothelial cell dysfunction. Am J Physiol Heart Circ Physiol. 2012;303:H189–96.
51. Napoli C, Martin-Padura I, de Nigris F, et al. Deletion of the p66Shc longevity gene reduces systemic and tissue oxidative stress, vascular cell apoptosis, and early atherogenesis in mice fed a high-fat diet. Proc Natl Acad Sci U S A. 2003;100:2112–6.
52. Kumar A, Kumar S, Vikram A, et al. Histone and DNA methylation-mediated epigenetic downregulation of endothelial Kruppel-like factor 2 by low-density lipoprotein cholesterol. Arterioscler Thromb Vasc Biol. 2013;33:1936–42.
53. Mitra S, Khaidakov M, Lu J, Ayyadevara S, et al. Prior exposure to oxidized low-density lipoprotein limits apoptosis in subsequent generations of endothelial cells by altering promoter methylation. Am J Physiol Heart Circ Physiol. 2011;301:H506–13.
54. Guay SP, Brisson D, Lamarche B, et al. DNA methylation variations at CETP and LPL gene promoter loci: new molecular biomarkers associated with blood lipid profile variability. Atherosclerosis. 2013;228:413–20.
55. Guay SP, Brisson D, Lamarche B, et al. Epipolymorphisms within lipoprotein genes contribute independently to plasma lipid levels in familial hypercholesterolemia. Epigenetics. 2014;9:718–29.
56. Newman PE. Can reduced folic acid and vitamin B12 levels cause deficient DNA methylation producing mutations which initiate atherosclerosis? Med Hypotheses. 1999;53:421–4.
57. Jamaluddin MD, Chen I, Yang F, et al. Homocysteine inhibits endothelial cell growth via DNA hypomethylation of the cyclin A gene. Blood. 2007;110:3648–55.
58. Sharma P, Kumar J, Garg G, et al. Detection of altered global DNA methylation in coronary artery disease patients. DNA Cell Biol. 2008;27:357–65.
59. Zaina S, Lindholm MW, Lund G. Nutrition and aberrant DNA methylation patterns in atherosclerosis: more than just hyperhomocysteinemia? J Nutr. 2005;135:5–8.
60. Zhu JH, Chen JZ, Wang XX, et al. Homocysteine accelerates senescence and reduces proliferation of endothelial progenitor cells. J Mol Cell Cardiol. 2006;40:648–52.
61. Richards JB, Valdes AM, Gardner JP, et al. Homocysteine levels and leukocyte telomere length. Atherosclerosis. 2008;200:271–7.
62. Zhang D, Wen X, Wu W, et al. Homocysteine-related hTERT DNA demethylation contributes to shortened leukocyte telomere length in atherosclerosis. Atherosclerosis. 2013;231:173–9.
63. Niu PP, Cao Y, Gong T, et al. Hypermethylation of DDAH2 promoter contributes to the dysfunction of endothelial progenitor cells in coronary artery disease patients. J Transl Med. 2014;12:170.
64. Zaina S, Heyn H, Carmona FJ, et al. A DNA methylation map of human atherosclerosis. Circ Cardiovasc Genet. 2014;7:692–700. An interesting study showing the gain of DNA methylation in atherosclerotic lesions emphasizing the opportunity to use demethylating agents for therapeutic benefit.
65. Li L, Xie J, Zhang M, Wang S. Homocysteine harasses the imprinting expression of IGF2 and H19 by demethylation of differentially methylated region between IGF2/H19 genes. Acta Biochim Biophys Sin (Shanghai). 2009;41:464–71.
66. Flowers E, Froelicher ES, Aouizerat BE. MicroRNA regulation of lipid metabolism. Metabolism. 2013;62:12–20. Relevant review on the topic of miRNAs as emergent players in lipid metabolism.
67. Rayner KJ, Esau CC, Hussain FN, et al. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature. 2011;478:404–7.
68. Iliopoulos D, Drosatos K, Hiyama Y, et al. MicroRNA-370 controls the expression of microRNA-122 and Cpt1alpha and affects lipid metabolism. J Lipid Res. 2010;51:1513–23.
69. Ramírez CM, Rotllan N, Vlassov AV, et al. Control of cholesterol metabolism and plasma high-density lipoprotein levels by microRNA-144. Circ Res. 2013;112:1592–601.
70. Kang MH, Zhang LH, Wijesekara N, et al. Regulation of ABCA1 protein expression and function in hepatic and pancreatic islet cells by miR-145. Arterioscler Thromb Vasc Biol. 2013;33:2724–32.
71. Zhao R, Feng J, He G. miR-613 regulates cholesterol efflux by targeting LXRα and ABCA1 in PPARγ activated THP-1 macrophages. Biochem Biophys Res Commun. 2014;448:329–34.
72. Ramirez CM, Dávalos A, Goedeke L, et al. MicroRNA-758 regulates cholesterol efflux through posttranscriptional repression of ATP-binding cassette transporter A1. Arterioscler Thromb Vasc Biol. 2011;31:2707–14.
73. Vickers KC, Landstreet SR, Levin MG, et al. MicroRNA-223 coordinates cholesterol homeostasis. Proc Natl Acad Sci U S A. 2014;111:14518–23.
74. Vinod M, Chennamsetty I, Colin S, et al. miR-206 controls LXRα expression and promotes LXR-mediated cholesterol efflux in macrophages. Biochim Biophys Acta. 2014;1841:827–35.
75. Zhang E, Wu Y. MicroRNAs: important modulators of oxLDL-mediated signaling in atherosclerosis. J Atheroscler Thromb. 2013;20:215–27.
76. Woollard KJ. Immunological aspects of atherosclerosis. Clin Sci (Lond). 2013;125:221–35.
77. Wierda RJ, Geutskens SB, Jukema JW, et al. Epigenetics in atherosclerosis and inflammation. J Cell Mol Med. 2010;14:1225–40.
78. Tao R, de Zoeten EF, Ozkaynak E, et al. Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat Med. 2007;13:1299–307.
79. Galkina E, Ley K. Immune and inflammatory mechanisms of atherosclerosis. Annu Rev Immunol. 2009;27:165–97.
80. Jia L, Zhu L, Wang JZ, et al. Methylation of FOXP3 in regulatory T cells is related to the severity of coronary artery disease. Atherosclerosis. 2013;228:346–52.
81. Sahinarslan A, Kocaman SA, Topal S, et al. The relation of serum monocyte chemoattractant protein-1 level with coronary atherosclerotic burden and collateral degree in stable coronary artery disease. Turk Kardiyol Dern Ars. 2011;39:269–75.
82. Wang J, Jiang Y, Yang A, et al. Hyperhomocysteinemia-induced monocyte chemoattractant protein-1 promoter DNA methylation by nuclear factor-κB/DNA methyltransferase 1 in apolipoprotein E-deficient mice. Biores Open Access. 2013;2:118–27.
83. Liu XL, Zhang PF, Ding SF, et al. Local gene silencing of monocyte chemoattractant protein-1 prevents vulnerable plaque disruption in apolipoprotein e-knockout mice. PLoS One. 2012;7:33497.
84. Choi JH, Nam KH, Kim J, et al. Trichostatin A exacerbates atherosclerosis in low density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2005;25:2404–9.
85. Okamoto H, Fujioka Y, Takahashi A, et al. Trichostatin A, an inhibitor of histone deacetylase, inhibits smooth muscle cell proliferation via induction of p21(WAF1). J Atheroscler Thromb. 2006;13:183–91.
86. Bekkering S, Quintin J, Joosten LA, et al. Oxidized low-density lipoprotein induces long-term proinflammatory cytokine production and foam cell formation via epigenetic reprogramming of monocytes. Arterioscler Thromb Vasc Biol. 2014;34:1731–8. This important study described the effect of oxLDL to induce a long-lasting proinflammatory phenotype in monocytes which accelerates atherosclerosis by proinflammatory cytokine production.
87. Ansel KM, Djuretic I, Tanasa B, Rao A. Regulation of Th2 differentiation and Il4 locus accessibility. Annu Rev Immunol. 2006;24:607–56.
88. Floess S, Freyer J, Siewert C, et al. Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol. 2007;5:38.
89. Wang B, Morinobu A, Horiuchi M, et al. Butyrate inhibits functional differentiation of human monocyte-derived dendritic cells. Cell Immunol. 2008;253:54–8.
90. Kong X, Fang M, Li P, et al. HDAC2 deacetylates class II transactivator and suppresses its activity in macrophages and smooth muscle cells. J Mol Cell Cardiol. 2009;46:292–9.
91. Zhou J, Wang KC, Wu W, et al. 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. 2011;108:10355–60.
92. Martin MM, Lee EJ, Buckenberger JA, Schmittgen TD, Elton TS. MicroRNA-155 regulates human angiotensin II type 1 receptor expression in fibroblasts. J Biol Chem. 2006;281:18277–84.
93. Schober A, Nazari-Jahantigh M, Wei Y, Bidzhekov K, et al. MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1. Nat Med. 2014;20:368–76. This study addresses interesting aspects of fow-dependent regulation of endothelial cell homeostasis. In addition the authors identified miR-126-5p and its target Dlk1 as major regulators of endothelial repair.
94. Wu XY, Fan WD, Fang R, Wu GF. Regulation of microRNA-155 in endothelial inflammation by targeting nuclear factor (NF)-κB P65. J Cell Biochem. 2014;115:1928–36.
95. Du F, Yu F, Wang Y, et al. MicroRNA-155 deficiency results in decreased macrophage inflammation and attenuated atherogenesis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2014;34:759–67.
96. Di Gregoli K, Jenkins N, Salter R, et al. MicroRNA-24 regulates macrophage behavior and retards atherosclerosis. Arterioscler Thromb Vasc Biol. 2014;34:1990–2000.
97. Fan X, Wang E, Wang X, et al. MicroRNA-21 is a unique signature associated with coronary plaque instability in humans by regulating matrix metalloproteinase-9 via reversion-inducing cysteine-rich protein with Kazal motifs. Exp Mol Pathol. 2014;96:242–9.
98. Napoli C. Developmental mechanisms involved in the primary prevention of atherosclerosis and cardiovascular disease. Curr Atheroscler Rep. 2011;13:170–5.