Epigenetic control of cardiovascular health by nutritional polyphenols involves multiple chromatin-modifying writer-reader-eraser proteins

Current Topics in Medicinal Chemistry

Volumn 16, Issue 7, 2016, Pages 788-806

  Declerck, Ken ^a   Szarc vel Szic, Katarzyna ^a   Palagani, Ajay ^a   Heyninck, Karen ^b   Haegeman, Guy ^b,c   Morand, Christine ^d,e   Milenkovic, Dragan ^d,e   Vanden Berghe, Wim ^a,b  

^a UNIVERSITY OF ANTWERP   (Belgium)

^b GHENT UNIVERSITY   (Belgium)

^c MAHIDOL UNIVERSITY   (Thailand)

^d CRNH AUVERGNE   (France)

^e UNIVERSITÉ CLERMONT AUVERGNE   (France)

Author keywords

Atherosclerosis; Chromatin modifying enzymes; Diet; DNA methylation; Epigenetics; Flavanols; Histone modifications; Writer reader eraser

Indexed keywords

ABC TRANSPORTER G1; ACTIVATING TRANSCRIPTION FACTOR 2; CHROMATIN MODIFYING WRITER READER ERASER PROTEIN; DNA METHYLTRANSFERASE 3A; GELATINASE A; GELATINASE B; GLUCOSE REGULATED PROTEIN 78; HISTONE DEACETYLASE 1; HISTONE DEACETYLASE 2; HISTONE DEACETYLASE 7; HOMOCYSTEINE; OXIDIZED LOW DENSITY LIPOPROTEIN; POLYPHENOL; REGULATOR PROTEIN; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; CHROMATIN; HISTONE;

ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; CELL DIFFERENTIATION; CHEMICAL STRUCTURE; CPG ISLAND; DNA METHYLATION; DOWN REGULATION; ENZYME ACTIVITY; EPIGENETICS; EXTRACELLULAR MATRIX; GENE EXPRESSION; GENE MUTATION; HISTONE MODIFICATION; HISTONE PHOSPHORYLATION; HUMAN; INFLAMMATION; LIPID DIET; NONHUMAN; PHENOTYPE; REVIEW; RISK FACTOR; UPREGULATION; ANIMAL; CARDIOVASCULAR FUNCTION; CHEMISTRY; CHROMATIN; DIET; DRUG EFFECTS; EDIBLE PLANT; GENETIC EPIGENESIS; GENETICS; HEALTH STATUS; ULTRASTRUCTURE;

ANIMALS; CARDIOVASCULAR PHYSIOLOGICAL PHENOMENA; CHROMATIN; DIET; EPIGENESIS, GENETIC; HEALTH STATUS; HISTONES; HUMANS; PLANTS, EDIBLE; POLYPHENOLS;

EID: 84983219829     PISSN: 15680266     EISSN: 18734294     Source Type: Journal    
DOI: 10.2174/1568026615666150825141720     Document Type: Review

References (236)

1. van Baak, M. A. Nutrition as a link between obesity and cardiovascular disease: how can we stop the obesity epidemic? Thromb. Haemost., 2013, 110 (4), 689-96.
2. Astrup, A. Healthy lifestyles in Europe: prevention of obesity and type II diabetes by diet and physical activity. Public Health Nutr., 2001, 4 (2B), 499-515.
3. Danaei, G.; Ding, E. L.; Mozaffarian, D.; Taylor, B.; Rehm, J.; Murray, C. J.; Ezzati, M. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med., 2009, 6 (4), e1000058.
4. Singhal, A. The global epidemic of noncommunicable disease: the role of early-life factors. Nestlé Nutr. Inst. Workshop Ser., 2014, 78, 123-32.
5. van Dijk, S. J.; Molloy, P. L.; Varinli, H.; Morrison, J. L.; Muhlhausler, B. S.; members of Epi, S., Epigenetics and human obesity. Int. J. Obes. (Lond.), 2014.
6. Burgio, E.; Lopomo, A.; Migliore, L. Obesity and diabetes: from genetics to epigenetics. Mol. Biol. Rep., 2014.
7. Martinez, J. A.; Milagro, F. I.; Claycombe, K. J.; Schalinske, K. L. Epigenetics in adipose tissue, obesity, weight loss, and diabetes. Adv. Nutr. Res., 2014, 5 (1), 71-81.
8. Sterns, J. D.; Smith, C. B.; Steele, J. R.; Stevenson, K. L.; Gallicano, G. I. Epigenetics and type II diabetes mellitus: underlying mechanisms of prenatal predisposition. Front. Cell Dev. Biol., 2014, 2, 15.
9. Ordovas, J. M.; Smith, C. E. Epigenetics and cardiovascular disease. Nat. Rev. Cardiol.,2010, 7 (9), 510-9.
10. Bannister, A. J.; Kouzarides, T. Regulation of chromatin by histone modifications. Cell Res., 2011, 21 (3), 381-95.
11. Arrowsmith, C. H.; Bountra, C.; Fish, P. V.; Lee, K.; Schapira, M., Epigenetic protein families: a new frontier for drug discovery. Nat. rev. Drug discov., 2012, 11 (5), 384-400.
12. Jeltsch, A.; Jurkowska, R. Z. New concepts in DNA methylation. Trends Biochem. Sci., 2014, 39 (7), 310-8.
13. Wilkinson, A. W.; Gozani, O. Histone-binding domains: strategies for discovery and characterization. Biochim. Biophys. Acta, 2014, 1839 (8), 669-75.
14. Sanchez, R.; Meslamani, J.; Zhou, M. M. The bromodomain: from epigenome reader to druggable target. Biochim. Biophys. Acta, 2014, 1839 (8), 676-85.
15. Yu, L.; Wang, Z.; Zhang, Z.; Ren, X.; Lu, X.; Ding, K. Smallmolecule BET inhibitors in clinical and preclinical development and their therapeutic potential. Curr. Top. Med. Chem., 2015, 15 (8), 776-94.
16. Ghosh, S.; Sati, S.; Sengupta, S.; Scaria, V. Distinct patterns of epigenetic marks and transcription factor binding sites across promoters of sense-intronic long noncoding RNAs. J. genet., 2015, 94 (1), 17-25.
17. Taguchi, Y. H. Apparent microRNA-Target-specific Histone Modification in Mammalian Spermatogenesis. Evol. Bioinform. Online, 2015, 11 (Suppl 1), 13-26.
18. Swierczynski, S.; Klieser, E.; Illig, R.; Alinger-Scharinger, B.; Kiesslich, T.; Neureiter, D. Histone deacetylation meets miRNA: epigenetics and post-transcriptional regulation in cancer and chronic diseases. Expert Opin. Biol. Ther., 2015, 15 (5), 651-64.
19. Osella, M.; Riba, A.; Testori, A.; Cora, D.; Caselle, M. Interplay of microRNA and epigenetic regulation in the human regulatory network. Front. Genet., 2014, 5, 345.
20. Mercer, T. R.; Mattick, J. S. Structure and function of long noncoding RNAs in epigenetic regulation. Nat. Struct. Mol. Biol., 2013, 20 (3), 300-7.
21. Xing, Z.; Lin, A.; Li, C.; Liang, K.; Wang, S.; Liu, Y.; Park, P. K.; Qin, L.; Wei, Y.; Hawke, D. H.; Hung, M. C.; Lin, C.; Yang, L. lncRNA directs cooperative epigenetic regulation downstream of chemokine signals. Cell, 2014, 159 (5), 1110-25.
22. Sato, F.; Tsuchiya, S.; Meltzer, S. J.; Shimizu, K. MicroRNAs and epigenetics. FEBS J., 2011, 278 (10), 1598-609.
23. Udali, S.; Guarini, P.; Moruzzi, S.; Choi, S. W.; Friso, S. Cardiovascular epigenetics: from DNA methylation to microRNAs. Mol. Aspects Med., 2013, 34 (4), 883-901.
24. Chen, T.; Dent, S. Y. Chromatin modifiers and remodellers: regulators of cellular differentiation. Nat. rev. Genet., 2014, 15 (2), 93-106.
25. Feil, R.; Fraga, M. F. Epigenetics and the environment: emerging patterns and implications. Nat. rev. Genet., 2011, 13 (2), 97-109.
26. Dunn, J.; Qiu, H.; Kim, S.; Jjingo, D.; Hoffman, R.; Kim, C. W.; Jang, I.; Son, D. J.; Kim, D.; Pan, C.; Fan, Y.; Jordan, I. K.; Jo, H. Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosis. J. Clin. Invest., 2014, 124 (7), 3187-99.
27. Jiang, Y. Z.; Jimenez, J. M.; Ou, K.; McCormick, M. E.; Zhang, L. D.; Davies, P. F. Hemodynamic disturbed flow induces differential DNA methylation of endothelial Kruppel-Like Factor 4 promoter in vitro and in vivo. Circ. Res., 2014, 115 (1), 32-43.
28. Chen, K. C.; Wang, Y. S.; Hu, C. Y.; Chang, W. C.; Liao, Y. C.; Dai, C. Y.; Juo, S. H. OxLDL up-regulates microRNA-29b, leading to epigenetic modifications of MMP-2/MMP-9 genes: a novel mechanism for cardiovascular diseases. FASEB J., 2011, 25 (5), 1718-28.
29. Turunen, M. P.; Aavik, E.; Yla-Herttuala, S. Epigenetics and atherosclerosis. Biochim. Biophys. Acta, 2009, 1790 (9), 886-91.
30. Liang, Y.; Yang, X.; Ma, L.; Cai, X.; Wang, L.; Yang, C.; Li, G.; Zhang, M.; Sun, W.; Jiang, Y. Homocysteine-mediated cholesterol efflux via ABCA1 and ACAT1 DNA methylation in THP-1 monocyte- derived foam cells. Acta Biochim. Biophys. Sin., 2013, 45 (3), 220-8.
31. Jiang, Y.; Zhang, H.; Sun, T.; Wang, J.; Sun, W.; Gong, H.; Yang, B.; Shi, Y.; Wei, J. The comprehensive effects of hyperlipidemia and hyperhomocysteinemia on pathogenesis of atherosclerosis and DNA hypomethylation in ApoE-/- mice. Acta Biochim. Biophys. Sin., 2012, 44 (10), 866-75.
32. Yu, X.; Ling, W.; Mi, M. Relationship of impairment induced by intracellular S-adenosylhomocysteine accumulation with DNA methylation in human umbilical vein endothelial cells treated with 3-deazaadenosine. Int. J. Exp. Pathol., 2009, 90 (6), 638-48.
33. Yideng, J.; Jianzhong, Z.; Ying, H.; Juan, S.; Jinge, Z.; Shenglan, W.; Xiaoqun, H.; Shuren, W. Homocysteine-mediated expression of SAHH, DNMTs, MBD2, and DNA hypomethylation potential pathogenic mechanism in VSMCs. DNA Cell Biol., 2007, 26 (8), 603-11.
34. Jiang, Y.; Sun, T.; Xiong, J.; Cao, J.; Li, G.; Wang, S. Hyperhomocysteinemia- mediated DNA hypomethylation and its potential epigenetic role in rats. Acta Biochim. Biophys. Sin., 2007, 39 (9), 657-67.
35. Xu, X.; Tan, X.; Tampe, B.; Nyamsuren, G.; Liu, X.; Maier, L. S.; Sossalla, S.; Kalluri, R.; Zeisberg, M.; Hasenfuss, G.; Zeisberg, E. M. Epigenetic balance of aberrant Rasal1 promoter methylation and hydroxymethylation regulates cardiac fibrosis. Cardiovasc. Res., 2015, 105 (3), 279-91.
36. Eom, G. H.; Kook, H. Posttranslational modifications of histone deacetylases: implications for cardiovascular diseases. Pharmacol. Ther., 2014, 143 (2), 168-80.
37. Dje N’Guessan, P.; Riediger, F.; Vardarova, K.; Scharf, S.; Eitel, J.; Opitz, B.; Slevogt, H.; Weichert, W.; Hocke, A. C.; Schmeck, B.; Suttorp, N.; Hippenstiel, S. Statins control oxidized LDL-mediated histone modifications and gene expression in cultured human endothelial cells. Arterioscler. Thromb. Vasc. Biol., 2009, 29 (3), 380-6.
38. Pandey, D.; Sikka, G.; Bergman, Y.; Kim, J. H.; Ryoo, S.; Romer, L.; Berkowitz, D. Transcriptional regulation of endothelial arginase 2 by histone deacetylase 2. Arterioscler. Thromb. Vasc. Biol., 2014, 34 (7), 1556-66.
39. Xiong, Y.; Yu, Y.; Montani, J. P.; Yang, Z.; Ming, X. F. Arginase- II induces vascular smooth muscle cell senescence and apoptosis through p66Shc and p53 independently of its l-arginine ureahydrolase activity: implications for atherosclerotic plaque vulnerability. J. Am. Heart Assoc., 2013, 2 (4), e000096.
40. Zheng, B.; Han, M.; Shu, Y. N.; Li, Y. J.; Miao, S. B.; Zhang, X. H.; Shi, H. J.; Zhang, T.; Wen, J. K. HDAC2 phosphorylationdependent Klf5 deacetylation and RARalpha acetylation induced by RAR agonist switch the transcription regulatory programs of p21 in VSMCs. Cell Res., 2011, 21 (10), 1487-508.
41. Martin, D.; Li, Y.; Yang, J.; Wang, G.; Margariti, A.; Jiang, Z.; Yu, H.; Zampetaki, A.; Hu, Y.; Xu, Q.; Zeng, L. Unspliced X-boxbinding Protein 1 (XBP1) Protects Endothelial Cells from Oxidative Stress through Interaction with Histone Deacetylase 3. J. Biol. Chem., 2014, 289 (44), 30625-34.
42. Zampetaki, A.; Zeng, L.; Margariti, A.; Xiao, Q.; Li, H.; Zhang, Z.; Pepe, A. E.; Wang, G.; Habi, O.; deFalco, E.; Cockerill, G.; Mason, J. C.; Hu, Y.; Xu, Q. Histone deacetylase 3 is critical in endothelial survival and atherosclerosis development in response to disturbed flow. Circulation, 2010, 121 (1), 132-42.
43. Hoeksema, M. A.; Gijbels, M. J.; Van den Bossche, J.; van der Velden, S.; Sijm, A.; Neele, A. E.; Seijkens, T.; Stoger, J. L.; Meiler, S.; Boshuizen, M. C.; Dallinga-Thie, G. M.; Levels, J. H.; Boon, L.; Mullican, S. E.; Spann, N. J.; Cleutjens, J. P.; Glass, C. K.; Lazar, M. A.; de Vries, C. J.; Biessen, E. A.; Daemen, M. J.; Lutgens, E.; de Winther, M. P. Targeting macrophage Histone deacetylase 3 stabilizes atherosclerotic lesions. EMBO Mol. Med., 2014, 6 (9), 1124-32.
44. Lanktree, M. B.; Hegele, R. A.; Yusuf, S.; Anand, S. S. Multiethnic genetic association study of carotid intima-media thickness using a targeted cardiovascular SNP microarray. Stroke, 2009, 40 (10), 3173-9.
45. Abu-Farha, M.; Tiss, A.; Abubaker, J.; Khadir, A.; Al-Ghimlas, F.; Al-Khairi, I.; Baturcam, E.; Cherian, P.; Elkum, N.; Hammad, M.; John, J.; Kavalakatt, S.; Warsame, S.; Behbehani, K.; Dermime, S.; Dehbi, M. Proteomics analysis of human obesity reveals the epigenetic factor HDAC4 as a potential target for obesity. PLoS One, 2013, 8 (9), e75342.
46. Usui, T.; Okada, M.; Mizuno, W.; Oda, M.; Ide, N.; Morita, T.; Hara, Y.; Yamawaki, H. HDAC4 mediates development of hypertension via vascular inflammation in spontaneous hypertensive rats. Am. J. Physiol. Heart Circ. Physiol., 2012, 302 (9), H1894-904.
47. Usui, T.; Morita, T.; Okada, M.; Yamawaki, H. Histone deacetylase 4 controls neointimal hyperplasia via stimulating proliferation and migration of vascular smooth muscle cells. Hypertension, 2014, 63 (2), 397-403.
48. Wang, W.; Ha, C. H.; Jhun, B. S.; Wong, C.; Jain, M. K.; Jin, Z. G. Fluid shear stress stimulates phosphorylation-dependent nuclear export of HDAC5 and mediates expression of KLF2 and eNOS. Blood, 2010, 115 (14), 2971-9.
49. Kwon, I. S.; Wang, W.; Xu, S.; Jin, Z. G. Histone deacetylase 5 interacts with Kruppel-like factor 2 and inhibits its transcriptional activity in endothelium. Cardiovasc. Res., 2014, 104 (1), 127-37.
50. Cunningham, K. S.; Gotlieb, A. I. The role of shear stress in the pathogenesis of atherosclerosis. Lab. Invest., 2005, 85 (1), 9-23.
51. Yan, Z. Q.; Yao, Q. P.; Zhang, M. L.; Qi, Y. X.; Guo, Z. Y.; Shen, B. R.; Jiang, Z. L. Histone deacetylases modulate vascular smooth muscle cell migration induced by cyclic mechanical strain. J. Biomech., 2009, 42 (7), 945-8.
52. Markus, H. S.; Makela, K. M.; Bevan, S.; Raitoharju, E.; Oksala, N.; Bis, J. C.; O’Donnell, C.; Hainsworth, A.; Lehtimaki, T. Evidence HDAC9 genetic variant associated with ischemic stroke increases risk via promoting carotid atherosclerosis. Stroke, 2013, 44 (5), 1220-5.
53. Azghandi, S.; Prell, C.; van der Laan, S. W.; Schneider, M.; Malik, R.; Berer, K.; Gerdes, N.; Pasterkamp, G.; Weber, C.; Haffner, C.; Dichgans, M. Deficiency of the Stroke Relevant HDAC9 Gene Attenuates Atherosclerosis in Accord With Allele-Specific Effects at 7p21.1. Stroke, 2014, 46(1), 197-202
54. International Stroke Genetics, C.; Wellcome Trust Case Control, C.; Bellenguez, C.; Bevan, S.; Gschwendtner, A.; Spencer, C. C.; Burgess, A. I.; Pirinen, M.; Jackson, C. A.; Traylor, M.; Strange, A.; Su, Z.; Band, G.; Syme, P. D.; Malik, R.; Pera, J.; Norrving, B.; Lemmens, R.; Freeman, C.; Schanz, R.; James, T.; Poole, D.; Murphy, L.; Segal, H.; Cortellini, L.; Cheng, Y. C.; Woo, D.; Nalls, M. A.; Muller-Myhsok, B.; Meisinger, C.; Seedorf, U.; Ross-Adams, H.; Boonen, S.; Wloch-Kopec, D.; Valant, V.; Slark, J.; Furie, K.; Delavaran, H.; Langford, C.; Deloukas, P.; Edkins, S.; Hunt, S.; Gray, E.; Dronov, S.; Peltonen, L.; Gretarsdottir, S.; Thorleifsson, G.; Thorsteinsdottir, U.; Stefansson, K.; Boncoraglio, G. B.; Parati, E. A.; Attia, J.; Holliday, E.; Levi, C.; Franzosi, M. G.; Goel, A.; Helgadottir, A.; Blackwell, J. M.; Bramon, E.; Brown, M. A.; Casas, J. P.; Corvin, A.; Duncanson, A.; Jankowski, J.; Mathew, C. G.; Palmer, C. N.; Plomin, R.; Rautanen, A.; Sawcer, S. J.; Trembath, R. C.; Viswanathan, A. C.; Wood, N. W.; Worrall, B. B.; Kittner, S. J.; Mitchell, B. D.; Kissela, B.; Meschia, J. F.; Thijs, V.; Lindgren, A.; Macleod, M. J.; Slowik, A.; Walters, M.; Rosand, J.; Sharma, P.; Farrall, M.; Sudlow, C. L.; Rothwell, P. M.; Dichgans, M.; Donnelly, P.; Markus, H. S. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nat. Genet., 2012, 44 (3), 328-33.
55. Dichgans, M.; Malik, R.; Konig, I. R.; Rosand, J.; Clarke, R.; Gretarsdottir, S.; Thorleifsson, G.; Mitchell, B. D.; Assimes, T. L.; Levi, C.; O’Donnell, C. J.; Fornage, M.; Thorsteinsdottir, U.; Psaty, B. M.; Hengstenberg, C.; Seshadri, S.; Erdmann, J.; Bis, J. C.; Peters, A.; Boncoraglio, G. B.; Marz, W.; Meschia, J. F.; Kathiresan, S.; Ikram, M. A.; McPherson, R.; Stefansson, K.; Sudlow, C.; Reilly, M. P.; Thompson, J. R.; Sharma, P.; Hopewell, J. C.; Chambers, J. C.; Watkins, H.; Rothwell, P. M.; Roberts, R.; Markus, H. S.; Samani, N. J.; Farrall, M.; Schunkert, H.; Consortium, M.; Consortium, C. A.; Consortium, C. D.; International Stroke Genetics, C. Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants. Stroke, 2014, 45 (1), 24-36.
56. Cao, Q.; Rong, S.; Repa, J. J.; St Clair, R.; Parks, J. S.; Mishra, N. Histone deacetylase 9 represses cholesterol efflux and alternatively activated macrophages in atherosclerosis development. Arterioscler. Thromb. Vasc. Biol., 2014, 34 (9), 1871-9.
57. Wei, J.; Gorman, T. E.; Liu, X.; Ith, B.; Tseng, A.; Chen, Z.; Simon, D. I.; Layne, M. D.; Yet, S. F. Increased neointima formation in cysteine-rich protein 2-deficient mice in response to vascular injury. Circ. Res., 2005, 97 (12), 1323-31.
58. Wu, M. L.; Chen, C. H.; Lin, Y. T.; Jheng, Y. J.; Ho, Y. C.; Yang, L. T.; Chen, L.; Layne, M. D.; Yet, S. F. Divergent signaling pathways cooperatively regulate TGFbeta induction of cysteine-rich protein 2 in vascular smooth muscle cells. Cell Commun. Signal: CCS, 2014, 12, 22.
59. Lin, D. W.; Chang, I. C.; Tseng, A.; Wu, M. L.; Chen, C. H.; Patenaude, C. A.; Layne, M. D.; Yet, S. F. Transforming growth factor beta up-regulates cysteine-rich protein 2 in vascular smooth muscle cells via activating transcription factor 2. J. Biol. Chem., 2008, 283 (22), 15003-14.
60. Fledderus, J. O.; van Thienen, J. V.; Boon, R. A.; Dekker, R. J.; Rohlena, J.; Volger, O. L.; Bijnens, A. P.; Daemen, M. J.; Kuiper, J.; van Berkel, T. J.; Pannekoek, H.; Horrevoets, A. J. Prolonged shear stress and KLF2 suppress constitutive proinflammatory transcription through inhibition of ATF2. Blood, 2007, 109 (10), 4249-57.
61. Cuhlmann, S.; Van der Heiden, K.; Saliba, D.; Tremoleda, J. L.; Khalil, M.; Zakkar, M.; Chaudhury, H.; Luong le, A.; Mason, J. C.; Udalova, I.; Gsell, W.; Jones, H.; Haskard, D. O.; Krams, R.; Evans, P. C. Disturbed blood flow induces RelA expression via c- Jun N-terminal kinase 1: a novel mode of NF-kappaB regulation that promotes arterial inflammation. Circ. Res., 2011, 108 (8), 950-9.
62. Buttice, G.; Miller, J.; Wang, L.; Smith, B. D. Interferon-gamma induces major histocompatibility class II transactivator (CIITA), which mediates collagen repression and major histocompatibility class II activation by human aortic smooth muscle cells. Circ. Res., 2006, 98 (4), 472-9.
63. Kong, X.; Fang, M.; Fang, F.; Li, P.; Xu, Y. PPARgamma enhances IFNgamma-mediated transcription and rescues the TGFbeta antagonism by stimulating CIITA in vascular smooth muscle cells. J. Mol. Cell. Cardiol., 2009, 46 (5), 748-57.
64. Kong, X.; Fang, M.; Li, P.; Fang, F.; Xu, Y. HDAC2 deacetylates class II transactivator and suppresses its activity in macrophages and smooth muscle cells. J. Mol. Cell. Cardiol., 2009, 46 (3), 292-9.
65. Soskic, S. S.; Dobutovic, B. D.; Sudar, E. M.; Obradovic, M. M.; Nikolic, D. M.; Zaric, B. L.; Stojanovic, S. D.; Stokic, E. J.; Mikhailidis, D. P.; Isenovic, E. R. Peroxisome proliferator-activated receptors and atherosclerosis. Angiology, 2011, 62 (7), 523-34.
66. Yuan, Y.; Xu, J. Loss-of-function deletion of the steroid receptor coactivator-1 gene in mice reduces estrogen effect on the vascular injury response. Arterioscler. Thromb. Vasc. Biol., 2007, 27 (7), 1521-7.
67. Yuan, Y.; Liao, L.; Tulis, D. A.; Xu, J. Steroid receptor coactivator- 3 is required for inhibition of neointima formation by estrogen. Circulation, 2002, 105 (22), 2653-9.
68. Li, H. J.; Haque, Z.; Lu, Q.; Li, L.; Karas, R.; Mendelsohn, M. Steroid receptor coactivator 3 is a coactivator for myocardin, the regulator of smooth muscle transcription and differentiation. Proc. Natl. Acad. Sci. U. S. A., 2007, 104 (10), 4065-70.
69. Kim, G. H.; Park, K.; Yeom, S. Y.; Lee, K. J.; Kim, G.; Ko, J.; Rhee, D. K.; Kim, Y. H.; Lee, H. K.; Kim, H. W.; Oh, G. T.; Lee, K. U.; Lee, J. W.; Kim, S. W. Characterization of ASC-2 as an antiatherogenic transcriptional coactivator of liver X receptors in macrophages. Mol. Endocrinol., 2009, 23 (7), 966-74.
70. Delerive, P.; De Bosscher, K.; Besnard, S.; Vanden Berghe, W.; Peters, J. M.; Gonzalez, F. J.; Fruchart, J. C.; Tedgui, A.; Haegeman, G.; Staels, B. Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1. J. Biol. Chem., 1999, 274 (45), 32048-54.
71. Vanden Berghe, W.; De Bosscher, K.; Boone, E.; Plaisance, S.; Haegeman, G. The nuclear factor-kappaB engages CBP/p300 and histone acetyltransferase activity for transcriptional activation of the interleukin-6 gene promoter. J. Biol. Chem., 1999, 274 (45), 32091-8.
72. Chen, L. F.; Greene, W. C. Regulation of distinct biological activities of the NF-kappaB transcription factor complex by acetylation. J. Mol. Med. (Berl.), 2003, 81 (9), 549-57.
73. Lu, Y.; Zhang, L.; Liao, X.; Sangwung, P.; Prosdocimo, D. A.; Zhou, G.; Votruba, A. R.; Brian, L.; Han, Y. J.; Gao, H.; Wang, Y.; Shimizu, K.; Weinert-Stein, K.; Khrestian, M.; Simon, D. I.; Freedman, N. J.; Jain, M. K. Kruppel-like factor 15 is critical for vascular inflammation. J. Clin. Invest., 2013, 123 (10), 4232-41
74. Chen, J.; Jiang, H.; Yang, J.; Chen, S. S.; Xu, L. Down-regulation of CREB-binding protein expression blocks thrombin-mediated endothelial activation by inhibiting acetylation of NF-kappaB. Int. J. Cardiol., 2012, 154 (2), 147-52.
75. Das, H.; Kumar, A.; Lin, Z.; Patino, W. D.; Hwang, P. M.; Feinberg, M. W.; Majumder, P. K.; Jain, M. K. Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes. Proc. Natl. Acad. Sci. U. S. A., 2006, 103 (17), 6653-8.
76. Weng, X.; Cheng, X.; Wu, X.; Xu, H.; Fang, M.; Xu, Y. Sin3B mediates collagen type I gene repression by interferon gamma in vascular smooth muscle cells. Biochem. Biophys. Res. Commun., 2014, 447 (2), 263-70.
77. Bouras, G.; Deftereos, S.; Tousoulis, D.; Giannopoulos, G.; Chatzis, G.; Tsounis, D.; Cleman, M. W.; Stefanadis, C. Asymmetric Dimethylarginine (ADMA): a promising biomarker for cardiovascular disease? Curr. Top. Med. Chem., 2013, 13 (2), 180-200.
78. Chen, X.; Niroomand, F.; Liu, Z.; Zankl, A.; Katus, H. A.; Jahn, L.; Tiefenbacher, C. P. Expression of nitric oxide related enzymes in coronary heart disease. Basic Res. Cardiol., 2006, 101 (4), 346-53.
79. Smith, C. L.; Anthony, S.; Hubank, M.; Leiper, J. M.; Vallance, P. Effects of ADMA upon gene expression: an insight into the pathophysiological significance of raised plasma ADMA. PLoS Med., 2005, 2 (10), e264.
80. Covic, M.; Hassa, P. O.; Saccani, S.; Buerki, C.; Meier, N. I.; Lombardi, C.; Imhof, R.; Bedford, M. T.; Natoli, G.; Hottiger, M. O. Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-kappaB-dependent gene expression. EMBO J., 2005, 24 (1), 85-96.
81. Sawicka, A.; Seiser, C. Histone H3 phosphorylation - a versatile chromatin modification for different occasions. Biochimie, 2012, 94 (11), 2193-201.
82. Rossetto, D.; Avvakumov, N.; Cote, J. Histone phosphorylation: a chromatin modification involved in diverse nuclear events. Epigenetics, 2012, 7 (10), 1098-108.
83. Li, F.; Adam, L.; Vadlamudi, R. K.; Zhou, H.; Sen, S.; Chernoff, J.; Mandal, M.; Kumar, R., p21-activated kinase 1 interacts with and phosphorylates histone H3 in breast cancer cells. EMBO Rep., 2002, 3 (8), 767-73.
84. Stockton, R. A.; Schaefer, E.; Schwartz, M. A. p21-activated kinase regulates endothelial permeability through modulation of contractility. J. Biol. Chem., 2004, 279 (45), 46621-30.
85. Orr, A. W.; Hahn, C.; Blackman, B. R.; Schwartz, M. A. p21- activated kinase signaling regulates oxidant-dependent NF-kappa B activation by flow. Circ. Res., 2008, 103 (6), 671-9.
86. Jhaveri, K. A.; Debnath, P.; Chernoff, J.; Sanders, J.; Schwartz, M. A. The role of p21-activated kinase in the initiation of atherosclerosis. BMC Cardiovasc. Disord., 2012, 12, 55.
87. Orr, A. W.; Stockton, R.; Simmers, M. B.; Sanders, J. M.; Sarembock, I. J.; Blackman, B. R.; Schwartz, M. A. Matrix-specific p21- activated kinase activation regulates vascular permeability in atherogenesis. J. Cell Biol., 2007, 176 (5), 719-27.
88. Komaravolu, R. K.; Adam, C.; Moonen, J. R.; Harmsen, M. C.; Goebeler, M.; Schmidt, M. Erk5 inhibits endothelial migration via KLF2-dependent down-regulation of PAK1. Cardiovasc. Res., 2014, 105(1):86-95
89. Zhang, X.; Mao, H.; Chen, J. Y.; Wen, S.; Li, D.; Ye, M.; Lv, Z. Increased expression of microRNA-221 inhibits PAK1 in endothelial progenitor cells and impairs its function via c-Raf/MEK/ERK pathway. Biochem. Biophys. Res. Commun., 2013, 431 (3), 404-8.
90. Hinoki, A.; Kimura, K.; Higuchi, S.; Eguchi, K.; Takaguri, A.; Ishimaru, K.; Frank, G. D.; Gerthoffer, W. T.; Sommerville, L. J.; Autieri, M. V.; Eguchi, S. p21-activated kinase 1 participates in vascular remodeling in vitro and in vivo. Hypertension, 2010, 55 (1), 161-5.
91. Weber, D. S.; Taniyama, Y.; Rocic, P.; Seshiah, P. N.; Dechert, M. A.; Gerthoffer, W. T.; Griendling, K. K. Phosphoinositidedependent kinase 1 and p21-activated protein kinase mediate reactive oxygen species-dependent regulation of platelet-derived growth factor-induced smooth muscle cell migration. Circ. Res., 2004, 94 (9), 1219-26.
92. Anand, P.; Brown, J. D.; Lin, C. Y.; Qi, J.; Zhang, R.; Artero, P. C.; Alaiti, M. A.; Bullard, J.; Alazem, K.; Margulies, K. B.; Cappola, T. P.; Lemieux, M.; Plutzky, J.; Bradner, J. E.; Haldar, S. M. BET bromodomains mediate transcriptional pause release in heart failure. Cell, 2013, 154 (3), 569-82.
93. Haldar, S. M.; McKinsey, T. A. BET-ting on chromatin-based therapeutics for heart failure. J. Mol. Cell. Cardiol., 2014, 74, 98-102.
94. Alvarez-Saavedra, M.; Carrasco, L.; Sura-Trueba, S.; Demarchi Aiello, V.; Walz, K.; Neto, J. X.; Young, J. I. Elevated expression of MeCP2 in cardiac and skeletal tissues is detrimental for normal development. Hum. Mol. Genet., 2010, 19 (11), 2177-90.
95. Panighini, A.; Duranti, E.; Santini, F.; Maffei, M.; Pizzorusso, T.; Funel, N.; Taddei, S.; Bernardini, N.; Ippolito, C.; Virdis, A.; Costa, M. Vascular dysfunction in a mouse model of Rett syndrome and effects of curcumin treatment. PLoS One, 2013, 8 (5), e64863.
96. Han, P.; Li, W.; Lin, C. H.; Yang, J.; Shang, C.; Nurnberg, S. T.; Jin, K. K.; Xu, W.; Lin, C. Y.; Lin, C. J.; Xiong, Y.; Chien, H. C.; Zhou, B.; Ashley, E.; Bernstein, D.; Chen, P. S.; Chen, H. S.; Quertermous, T.; Chang, C. P. A long noncoding RNA protects the heart from pathological hypertrophy. Nature, 2014, 514 (7520), 102-6.
97. Thum, T.; Condorelli, G. Long noncoding RNAs and microRNAs in cardiovascular pathophysiology. Circ. Res., 2015, 116 (4), 751-62.
98. McKinsey, T. A. Targeting inflammation in heart failure with histone deacetylase inhibitors. Mol. Med., 2011, 17 (5-6), 434-41.
99. McKinsey, T. A. Therapeutic potential for HDAC inhibitors in the heart. Annu. Rev. Pharmacol. Toxicol., 2012, 52, 303-19.
100. Xie, M.; Hill, J. A. HDAC-dependent ventricular remodeling. Trends Cardiovasc. Med., 2013, 23 (6), 229-35.
101. Byrne, M. M.; Murphy, R. T.; Ryan, A. W. Epigenetic modulation in the treatment of atherosclerotic disease. Front. Genet., 2014, 5, 364.
102. Dawson, M. A.; Kouzarides, T. Cancer epigenetics: from mechanism to therapy. Cell, 2012, 150 (1), 12-27.
103. Portela, A.; Esteller, M. Epigenetic modifications and human disease. Nat. Biotechnol., 2010, 28 (10), 1057-68.
104. Marian, A. J. Elements of ’missing heritability’. Curr. Opin. Cardiol., 2012, 27 (3), 197-201.
105. Wierda, R. J.; Rietveld, I. M.; van Eggermond, M. C.; Belien, J. A.; van Zwet, E. W.; Lindeman, J. H.; van den Elsen, P. J. Global histone H3 lysine 27 triple methylation levels are reduced in vessels with advanced atherosclerotic plaques. Life Sci., 2014.
106. Zaina, S.; Heyn, H.; Carmona, F. J.; Varol, N.; Sayols, S.; Condom, E.; Ramirez-Ruz, J.; Gomez, A.; Goncalves, I.; Moran, S.; Esteller, M. DNA methylation map of human atherosclerosis. Circ. Cardiovasc. Genet., 2014, 7 (5), 692-700.
107. Libby, P.; Ridker, P. M.; Hansson, G. K. Progress and challenges in translating the biology of atherosclerosis. Nature, 2011, 473 (7347), 317-25.
108. Bornfeldt, K. E.; Tabas, I. Insulin resistance, hyperglycemia, and atherosclerosis. Cell metabol., 2011, 14 (5), 575-85.
109. Barton, M. Cholesterol and atherosclerosis: modulation by oestrogen. Curr. Opin. Lipidol., 2013, 24 (3), 214-20.
110. Guthikonda, S.; Haynes, W. G. Homocysteine: role and implications in atherosclerosis. Curr. Atheroscler. Rep., 2006, 8 (2), 100-6.
111. Peiffer, V.; Sherwin, S. J.; Weinberg, P. D. Does low and oscillatory wall shear stress correlate spatially with early atherosclerosis? A systematic review. Cardiovasc. Res., 2013, 99 (2), 242-50.
112. Hollander, W. Role of hypertension in atherosclerosis and cardiovascular disease. Am. J. Cardiol., 1976, 38 (6), 786-800.
113. Rocha, V. Z.; Libby, P. Obesity, inflammation, and atherosclerosis. Nat. Rev. Cardiol., 2009, 6 (6), 399-409.
114. Van den Bossche, J.; Neele, A. E.; Hoeksema, M. A.; de Winther, M. P. Macrophage polarization: the epigenetic point of view. Curr. Opin. Lipidol., 2014, 25 (5), 367-73.
115. Findeisen, H. M.; Kahles, F. K.; Bruemmer, D. Epigenetic regulation of vascular smooth muscle cell function in atherosclerosis. Curr. atheroscler. rep., 2013, 15 (5), 319.
116. Xu, Y. Transcriptional regulation of endothelial dysfunction in atherosclerosis: an epigenetic perspective. J. biomed. res., 2014, 28 (1), 47-52.
117. Zawadzki, C.; Chatelain, N.; Delestre, M.; Susen, S.; Quesnel, B.; Juthier, F.; Jeanpierre, E.; Azzaoui, R.; Corseaux, D.; Breyne, J.; Torpier, G.; Staels, B.; Van Belle, E.; Jude, B. Tissue factor pathway inhibitor-2 gene methylation is associated with low expression in carotid atherosclerotic plaques. Atherosclerosis, 2009, 204 (2), e4-14.
118. Post, W. S.; Goldschmidt-Clermont, P. J.; Wilhide, C. C.; Heldman, A. W.; Sussman, M. S.; Ouyang, P.; Milliken, E. E.; Issa, J. P. Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system. Cardiovasc. Res., 1999, 43 (4), 985-91.
119. Kim, J.; Kim, J. Y.; Song, K. S.; Lee, Y. H.; Seo, J. S.; Jelinek, J.; Goldschmidt-Clermont, P. J.; Issa, J. P. Epigenetic changes in estrogen receptor beta gene in atherosclerotic cardiovascular tissues and in-vitro vascular senescence. Biochim. Biophys. Acta, 2007, 1772 (1), 72-80.
120. Niu, P. P.; Cao, Y.; Gong, T.; Guo, J. H.; Zhang, B. K.; Jia, S. J. Hypermethylation of DDAH2 promoter contributes to the dysfunction of endothelial progenitor cells in coronary artery disease patients. J. Transl. Med., 2014, 12, 170.
121. Ekstrand, J.; Razuvaev, A.; Folkersen, L.; Roy, J.; Hedin, U. Tissue factor pathway inhibitor-2 is induced by fluid shear stress in vascular smooth muscle cells and affects cell proliferation and survival. J. Vasc. Surg., 2010, 52 (1), 167-75.
122. Pou, J.; Rebollo, A.; Piera, L.; Merlos, M.; Roglans, N.; Laguna, J. C.; Alegret, M. Tissue factor pathway inhibitor 2 is induced by thrombin in human macrophages. Biochim. Biophys. Acta, 2011, 1813 (6), 1254-60.
123. Huang, Y.; Peng, K.; Su, J.; Huang, Y.; Xu, Y.; Wang, S. Different effects of homocysteine and oxidized low density lipoprotein on methylation status in the promoter region of the estrogen receptor alpha gene. Acta Biochim. Biophys. Sin., 2007, 39 (1), 19-26.
124. Huang, Y. S.; Zhi, Y. F.; Wang, S. R. Hypermethylation of estrogen receptor-alpha gene in atheromatosis patients and its correlation with homocysteine. Pathophysiology, 2009, 16 (4), 259-65.
125. Guay, S. P.; Legare, C.; Houde, A. A.; Mathieu, P.; Bosse, Y.; Bouchard, L. Acetylsalicylic acid, aging and coronary artery disease are associated with ABCA1 DNA methylation in men. Clin. Epigenet., 2014, 6 (1), 14.
126. Guay, S. P.; Brisson, D.; Munger, J.; Lamarche, B.; Gaudet, D.; Bouchard, L. ABCA1 gene promoter DNA methylation is associated with HDL particle profile and coronary artery disease in familial hypercholesterolemia. Epigenetics, 2012, 7 (5), 464-72.
127. Buechler, C.; Bauer, S. ATP binding cassette transporter A1 (ABCA1) associated proteins: potential drug targets in the metabolic syndrome and atherosclerotic disease? Curr. Pharm. Biotechnol., 2012, 13 (2), 319-30.
128. Jiang, D.; Zheng, D.; Wang, L.; Huang, Y.; Liu, H.; Xu, L.; Liao, Q.; Liu, P.; Shi, X.; Wang, Z.; Sun, L.; Zhou, Q.; Li, N.; Xu, L.; Le, Y.; Ye, M.; Shao, G.; Duan, S. Elevated PLA2G7 gene promoter methylation as a gender-specific marker of aging increases the risk of coronary heart disease in females. PLoS One, 2013, 8 (3), e59752.
129. Rosenson, R. S.; Stafforini, D. M. Modulation of oxidative stress, inflammation, and atherosclerosis by lipoprotein-associated phospholipase A2. J. Lipid Res., 2012, 53 (9), 1767-82.
130. Cai, A.; Zheng, D.; Qiu, R.; Mai, W.; Zhou, Y. Lipoproteinassociated phospholipase A2 (Lp-PLA(2)): a novel and promising biomarker for cardiovascular risks assessment. Dis. Markers, 2013, 34 (5), 323-31.
131. Zhao, J.; Forsberg, C. W.; Goldberg, J.; Smith, N. L.; Vaccarino, V. MAOA promoter methylation and susceptibility to carotid atherosclerosis: role of familial factors in a monozygotic twin sample. BMC Med. Genet., 2012, 13, 100.
132. Breton, C. V.; Park, C.; Siegmund, K.; Gauderman, W. J.; Whitfield- Maxwell, L.; Hodis, H. N.; Avol, E.; Gilliland, F. D. NOS1 methylation and carotid artery intima-media thickness in children. Circ. Cardiovasc. Genet., 2014, 7 (2), 116-22.
133. Zaina, S.; Heyn, H.; Carmona, F. J.; Varol, N.; Sayols, S.; Condom, E.; Ramirez-Ruz, J.; Gomez, A.; Goncalves, I.; Moran, S.; Esteller, M. A DNA Methylation Map of Human Atherosclerosis. Circ. Cardiovasc. genet.,2014, 7(5):692-700.
134. Park, Y. J.; Claus, R.; Weichenhan, D.; Plass, C. Genome-wide epigenetic modifications in cancer. Prog. Drug Res., 2011, 67, 25-49.
135. Nazarenko, M. S.; Markov, A. V.; Lebedev, I. N.; Freidin, M. B.; Sleptcov, A. A.; Koroleva, I. A.; Frolov, A. V.; Popov, V. A.; Barbarash, O. L.; Puzyrev, V. P. A Comparison of Genome-Wide DNA Methylation Patterns between Different Vascular Tissues from Patients with Coronary Heart Disease. PLoS One, 2015, 10 (4), e0122601.
136. Sharma, P.; Kumar, J.; Garg, G.; Kumar, A.; Patowary, A.; Karthikeyan, G.; Ramakrishnan, L.; Brahmachari, V.; Sengupta, S. Detection of altered global DNA methylation in coronary artery disease patients. DNA Cell Biol., 2008, 27 (7), 357-65.
137. Sharma, P.; Garg, G.; Kumar, A.; Mohammad, F.; Kumar, S. R.; Tanwar, V. S.; Sati, S.; Sharma, A.; Karthikeyan, G.; Brahmachari, V.; Sengupta, S. Genome wide DNA methylation profiling for epigenetic alteration in coronary artery disease patients. Gene, 2014, 541 (1), 31-40.
138. Kim, M.; Long, T. I.; Arakawa, K.; Wang, R.; Yu, M. C.; Laird, P. W. DNA methylation as a biomarker for cardiovascular disease risk. PLoS One, 2010, 5 (3), e9692.
139. Castillo-Diaz, S. A.; Garay-Sevilla, M. E.; Hernandez-Gonzalez, M. A.; Solis-Martinez, M. O.; Zaina, S. Extensive demethylation of normally hypermethylated CpG islands occurs in human atherosclerotic arteries. Int. J. Mol. Med., 2010, 26 (5), 691-700.
140. Aavik, E.; Lumivuori, H.; Leppanen, O.; Wirth, T.; Hakkinen, S. K.; Brasen, J. H.; Beschorner, U.; Zeller, T.; Braspenning, M.; van Criekinge, W.; Makinen, K.; Yla-Herttuala, S. Global DNA methylation analysis of human atherosclerotic plaques reveals extensive genomic hypomethylation and reactivation at imprinted locus 14q32 involving induction of a miRNA cluster. Eur. Heart J., 2015, 36 (16), 993-1000.
141. Hiltunen, M. O.; Turunen, M. P.; Hakkinen, T. P.; Rutanen, J.; Hedman, M.; Makinen, K.; Turunen, A. M.; Aalto-Setala, K.; Yla- Herttuala, S. DNA hypomethylation and methyltransferase expression in atherosclerotic lesions. Vasc. Med., 2002, 7 (1), 5-11.
142. Castro, R.; Rivera, I.; Struys, E. A.; Jansen, E. E.; Ravasco, P.; Camilo, M. E.; Blom, H. J.; Jakobs, C.; Tavares de Almeida, I. Increased homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease. Clin. Chem., 2003, 49 (8), 1292-6.
143. Krishna, S. M.; Dear, A.; Craig, J. M.; Norman, P. E.; Golledge, J. The potential role of homocysteine mediated DNA methylation and associated epigenetic changes in abdominal aortic aneurysm formation. Atherosclerosis, 2013, 228 (2), 295-305.
144. Lee, M. E.; Wang, H. Homocysteine and hypomethylation. A novel link to vascular disease. Trends Cardiovasc. Med., 1999, 9 (1-2), 49-54.
145. Yang, X. L.; Tian, J.; Liang, Y.; Ma, C. J.; Yang, A. N.; Wang, J.; Ma, S. C.; Cheng, Y.; Hua, X.; Jiang, Y. D. Homocysteine induces blood vessel global hypomethylation mediated by LOX-1. Genet. mol. res.: GMR 2014, 13 (2), 3787-99.
146. Liu, C.; Wang, Q.; Guo, H.; Xia, M.; Yuan, Q.; Hu, Y.; Zhu, H.; Hou, M.; Ma, J.; Tang, Z.; Ling, W. Plasma Sadenosylhomocysteine is a better biomarker of atherosclerosis than homocysteine in apolipoprotein E-deficient mice fed high dietary methionine. J. Nutr., 2008, 138 (2), 311-5.
147. Castro, R.; Rivera, I.; Martins, C.; Struys, E. A.; Jansen, E. E.; Clode, N.; Graca, L. M.; Blom, H. J.; Jakobs, C.; de Almeida, I. T. Intracellular S-adenosylhomocysteine increased levels are associated with DNA hypomethylation in HUVEC. J. Mol. Med. (Berl.), 2005, 83 (10), 831-6.
148. Yang, T. C.; Chen, Y. J.; Chang, S. F.; Chen, C. H.; Chang, P. Y.; Lu, S. C. Malondialdehyde mediates oxidized LDL-induced coronary toxicity through the Akt-FGF2 pathway via DNA methylation. J. Biomed. Sci., 2014, 21, 11.
149. Jia, L.; Zhu, L.; Wang, J. Z.; Wang, X. J.; Chen, J. Z.; Song, L.; Wu, Y. J.; Sun, K.; Yuan, Z. Y.; Hui, R. Methylation of FOXP3 in regulatory T cells is related to the severity of coronary artery disease. Atherosclerosis, 2013, 228 (2), 346-52.
150. Mitra, S.; Khaidakov, M.; Lu, J.; Ayyadevara, S.; Szwedo, J.; Wang, X. W.; Chen, C.; Khaidakov, S.; Kasula, S. R.; Stone, A.; Pogribny, I.; Mehta, J. L. 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 (2), H506-13.
151. Alkemade, F. E.; van Vliet, P.; Henneman, P.; van Dijk, K. W.; Hierck, B. P.; van Munsteren, J. C.; Scheerman, J. A.; Goeman, J. J.; Havekes, L. M.; Gittenberger-de Groot, A. C.; van den Elsen, P. J.; DeRuiter, M. C. Prenatal exposure to apoE deficiency and postnatal hypercholesterolemia are associated with altered cell-specific lysine methyltransferase and histone methylation patterns in the vasculature. Am. J. Pathol., 2010, 176 (2), 542-8.
152. Bekkering, S.; Quintin, J.; Joosten, L. A.; van der Meer, J. W.; Netea, M. G.; Riksen, N. P. 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 (8), 1731-8.
153. Zhang, H.; Park, Y.; Wu, J.; Chen, X.; Lee, S.; Yang, J.; Dellsperger, K. C.; Zhang, C. Role of TNF-alpha in vascular dysfunction. Clin. Sci. (Lond.), 2009, 116 (3), 219-30.
154. Lin, J.; Kakkar, V.; Lu, X. Impact of MCP-1 in atherosclerosis. Curr. Pharm. Des., 2014, 20 (28), 4580-8.
155. Apostolakis, S.; Vogiatzi, K.; Amanatidou, V.; Spandidos, D. A. Interleukin 8 and cardiovascular disease. Cardiovasc. Res., 2009, 84 (3), 353-60.
156. Hartman, J.; Frishman, W. H. Inflammation and atherosclerosis: a review of the role of interleukin-6 in the development of atherosclerosis and the potential for targeted drug therapy. Cardiol. Rev., 2014, 22 (3), 147-51.
157. Lin, J.; Kakkar, V.; Lu, X. Impact of matrix metalloproteinases on atherosclerosis. Curr. Drug Targets, 2014, 15 (4), 442-53.
158. Kelley, J. L.; Ozment, T. R.; Li, C.; Schweitzer, J. B.; Williams, D. L. Scavenger receptor-A (CD204): a two-edged sword in health and disease. Crit. Rev. Immunol., 2014, 34 (3), 241-61.
159. Park, Y. M., CD36, a scavenger receptor implicated in atherosclerosis. Exp. Mol. Med. 2014, 46, e99.
160. Fang, F.; Yang, Y.; Yuan, Z.; Gao, Y.; Zhou, J.; Chen, Q.; Xu, Y. Myocardin-related transcription factor A mediates OxLDL-induced endothelial injury. Circ. Res., 2011, 108 (7), 797-807.
161. Zawada, A. M.; Rogacev, K. S.; Hummel, B.; Berg, J. T.; Friedrich, A.; Roth, H. J.; Obeid, R.; Geisel, J.; Fliser, D.; Heine, G. H. S-adenosylhomocysteine is associated with subclinical atherosclerosis and renal function in a cardiovascular low-risk population. Atherosclerosis, 2014, 234 (1), 17-22.
162. Xiao, Y.; Huang, W.; Zhang, J.; Peng, C.; Xia, M.; Ling, W. Increased Plasma S-Adenosylhomocysteine-Accelerated Atherosclerosis Is Associated With Epigenetic Regulation of Endoplasmic Reticulum Stress in apoE-/- Mice. Arterioscler. Thromb. Vasc. Biol., 2014.
163. Chistiakov, D. A.; Sobenin, I. A.; Orekhov, A. N.; Bobryshev, Y. V. Role of endoplasmic reticulum stress in atherosclerosis and diabetic macrovascular complications. BioMed. Res. Int., 2014, 2014, 610140.
164. Illi, B.; Nanni, S.; Scopece, A.; Farsetti, A.; Biglioli, P.; Capogrossi, M. C.; Gaetano, C. Shear stress-mediated chromatin remodeling provides molecular basis for flow-dependent regulation of gene expression. Circ. Res., 2003, 93 (2), 155-61.
165. Bayarsaihan, D. Epigenetic mechanisms in inflammation. J. Dent. Res., 2011, 90 (1), 9-17.
166. Jimenez-Chillaron, J. C.; Diaz, R.; Martinez, D.; Pentinat, T.; Ramon-Krauel, M.; Ribo, S.; Plosch, T. The role of nutrition on epigenetic modifications and their implications on health. Biochimie, 2012, 94 (11), 2242-63.
167. Barker, D. J. The developmental origins of chronic adult disease. Acta Paediatr. Suppl., 2004, 93 (446), 26-33.
168. Osborne-Majnik, A.; Fu, Q.; Lane, R. H. Epigenetic mechanisms in fetal origins of health and disease. Clin. Obstet. Gynecol., 2013, 56 (3), 622-32.
169. Milenkovic, D.; Vanden Berghe, W.; Boby, C.; Leroux, C.; Declerck, K.; Szarc vel Szic, K.; Heyninck, K.; Laukens, K.; Bizet, M.; Defrance, M.; Dedeurwaerder, S.; Calonne, E.; Fuks, F.; Haegeman, G.; Haenen, G. R.; Bast, A.; Weseler, A. R. Dietary flavanols modulate the transcription of genes associated with cardiovascular pathology without changes in their DNA methylation state. PLoS One, 2014, 9 (4), e95527.
170. Lim, J. P.; Brunet, A. Bridging the transgenerational gap with epigenetic memory. Trends Genet., 2013, 29 (3), 176-86.
171. Milagro, F. I.; Mansego, M. L.; De Miguel, C.; Martinez, J. A. Dietary factors, epigenetic modifications and obesity outcomes: progresses and perspectives. Mol. Aspects Med., 2013, 34 (4), 782-812.
172. Vanden Berghe, W. Epigenetic impact of dietary polyphenols in cancer chemoprevention: lifelong remodeling of our epigenomes. Pharmacol. Res., 2012, 65 (6), 565-76.
173. Remely, M.; Lovrecic, L.; de la Garza, A. L.; Migliore, L.; Peterlin, B.; Milagro, F. I.; Martinez, A. J.; Haslberger, A. G. Therapeutic perspectives of epigenetically active nutrients. Br. J. Pharmacol., 2014.
174. Alkemade, F. E.; Gittenberger-de Groot, A. C.; Schiel, A. E.; VanMunsteren, J. C.; Hogers, B.; van Vliet, L. S.; Poelmann, R. E.; Havekes, L. M.; Willems van Dijk, K.; DeRuiter, M. C. Intrauterine exposure to maternal atherosclerotic risk factors increases the susceptibility to atherosclerosis in adult life. Arterioscler. Thromb. Vasc. Biol., 2007, 27 (10), 2228-35.
175. van Kampen, E.; Jaminon, A.; van Berkel, T. J.; Van Eck, M. Dietinduced (epigenetic) changes in bone marrow augment atherosclerosis. J. Leukoc. Biol., 2014, 96 (5), 833-41.
176. Ceriello, A. The emerging challenge in diabetes: the “metabolic memory”. Vascul. Pharmacol., 2012, 57 (5-6), 133-8.
177. Reddy, M. A.; Natarajan, R. Epigenetic mechanisms in diabetic vascular complications. Cardiovasc. Res., 2011, 90 (3), 421-9.
178. Netea, M. G.; Quintin, J.; van der Meer, J. W. Trained immunity: a memory for innate host defense. Cell host microbe., 2011, 9 (5), 355-61.
179. Quintin, J.; Saeed, S.; Martens, J. H.; Giamarellos-Bourboulis, E. J.; Ifrim, D. C.; Logie, C.; Jacobs, L.; Jansen, T.; Kullberg, B. J.; Wijmenga, C.; Joosten, L. A.; Xavier, R. J.; van der Meer, J. W.; Stunnenberg, H. G.; Netea, M. G. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell host microbe., 2012, 12 (2), 223-32.
180. Bekkering, S.; Joosten, L. A.; van der Meer, J. W.; Netea, M. G.; Riksen, N. P. Trained innate immunity and atherosclerosis. Curr. Opin. Lipidol., 2013, 24 (6), 487-92.
181. Heiss, C.; Keen, C. L.; Kelm, M. Flavanols and cardiovascular disease prevention. Eur. Heart J., 2010, 31 (21), 2583-92.
182. Ottaviani, J. I.; Momma, T. Y.; Kuhnle, G. K.; Keen, C. L.; Schroeter, H., Structurally related (-)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic standards. Free Radic. Biol. Med. 2012, 52 (8), 1403-12.
183. Reker, D.; Perna, A. M.; Rodrigues, T.; Schneider, P.; Reutlinger, M.; Monch, B.; Koeberle, A.; Lamers, C.; Gabler, M.; Steinmetz, H.; Muller, R.; Schubert-Zsilavecz, M.; Werz, O.; Schneider, G., Revealing the macromolecular targets of complex natural products. Nat. Chem. 2014, 6 (12), 1072-8.
184. Messner, B.; Bernhard, D., Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler. Thromb. Vasc. Biol. 2014, 34 (3), 509-15.
185. Jimenez, R.; Duarte, J.; Perez-Vizcaino, F. Epicatechin: endothelial function and blood pressure. J. Agric. Food Chem., 2012, 60 (36), 8823-30.
186. Claude, S.; Boby, C.; Rodriguez-Mateos, A.; Spencer, J. P.; Gerard, N.; Morand, C.; Milenkovic, D. Flavanol metabolites reduce monocyte adhesion to endothelial cells through modulation of expression of genes via p38-MAPK and p65-Nf-kB pathways. Mol. nutri. food res., 2014, 58 (5), 1016-27.
187. Dolinoy, D. C.; Weidman, J. R.; Waterland, R. A.; Jirtle, R. L. Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ. Health Perspect, 2006, 114 (4), 567-72.
188. Dolinoy, D. C.; Huang, D.; Jirtle, R. L. Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc. Natl. Acad. Sci. U. S. A., 2007, 104 (32), 13056-61.
189. Fang, M. Z.; Wang, Y.; Ai, N.; Hou, Z.; Sun, Y.; Lu, H.; Welsh, W.; Yang, C. S. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res., 2003, 63 (22), 7563-70.
190. Hsieh, H. Y.; Chiu, P. H.; Wang, S. C. Histone modifications and traditional Chinese medicinals. BMC Complement. Altern. Med., 2013, 13, 115.
191. Hsieh, H. Y.; Chiu, P. H.; Wang, S. C. Epigenetics in traditional chinese pharmacy: a bioinformatic study at pharmacopoeia scale. Evid. Based Complement. Alternat. Med., 2011, 2011, 816714.
192. Szarc vel Szic, K.; Ndlovu, M. N.; Haegeman, G.; Vanden Berghe, W. Nature or nurture: let food be your epigenetic medicine in chronic inflammatory disorders. Biochem. Pharmacol., 2010, 80 (12), 1816-32.
193. Szarc vel Szic, K.; Op de Beeck, K.; Ratman, D.; Wouters, A.; Beck, I. M.; Declerck, K.; Heyninck, K.; Fransen, E.; Bracke, M.; De Bosscher, K.; Lardon, F.; Van Camp, G.; Vanden Berghe, W. Pharmacological levels of Withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells. PLoS One, 2014, 9 (2), e87850.
194. Bast, A.; Claude, S.; Haegeman, G.; Haenen, G.; Heiss, C.; Heyninck, K.; Merx, M.; Milenkovic, D.; Morand, C.; Ruijters, E.; Vanden Berghe, W.; Weseler, A. Flavanols: what do we know about their mechanisms of action? Free Radic. Biol. Med., 2012, 53 (Suppl2), S13.
195. Zhang, L. X.; DeNicola, M.; Qin, X.; Du, J.; Ma, J.; Tina Zhao, Y.; Zhuang, S.; Liu, P. Y.; Wei, L.; Qin, G.; Tang, Y.; Zhao, T. C. Specific inhibition of HDAC4 in cardiac progenitor cells enhances myocardial repairs. Am. J. Physiol. Cell Physiol., 2014, 307 (4), C358-72.
196. Azghandi, S.; Prell, C.; van der Laan, S. W.; Schneider, M.; Malik, R.; Berer, K.; Gerdes, N.; Pasterkamp, G.; Weber, C.; Haffner, C.; Dichgans, M. Deficiency of the Stroke Relevant HDAC9 Gene Attenuates Atherosclerosis in Accord With Allele-Specific Effects at 7p21.1. Stroke, 2015, 46 (1), 197-202.
197. Sarajlic, A.; Gligorijevic, V.; Radak, D.; Przulj, N. Network wiring of pleiotropic kinases yields insight into protective role of diabetes on aneurysm. Integr. Biol. (Camb.), 2014, 6 (11), 1049-57.
198. Kang, I.; Okla, M.; Chung, S. Ellagic acid inhibits adipocyte differentiation through coactivator-associated arginine methyltransferase 1-mediated chromatin modification. J. nutr. biochem., 2014, 25 (9), 946-53.
199. Prasad, R.; Katiyar, S. K. Polyphenols from green tea inhibit the growth of melanoma cells through inhibition of class I histone deacetylases and induction of DNA damage. Genes Cancer, 2015, 6 (1-2), 49-61.
200. Deb, G.; Thakur, V. S.; Limaye, A. M.; Gupta, S. Epigenetic induction of tissue inhibitor of matrix metalloproteinase-3 by green tea polyphenols in breast cancer cells. Mol. Carcinog., 2015, 54 (6), 485-99.
201. Liu, H. L.; Chen, Y.; Cui, G. H.; Zhou, J. F. Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raji proliferation. Acta Pharmacol. Sin., 2005, 26 (5), 603-9.
202. Busbee, P. B.; Nagarkatti, M.; Nagarkatti, P. S. Natural indoles, indole-3-carbinol and 3,3’-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression. Toxicol. Appl. Pharmacol., 2014, 274 (1), 7-16.
203. Clarke, J. D.; Hsu, A.; Yu, Z.; Dashwood, R. H.; Ho, E. Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells. Mol. nutr. food res., 2011, 55 (7), 999-1009.
204. Rajendran, P.; Delage, B.; Dashwood, W. M.; Yu, T. W.; Wuth, B.; Williams, D. E.; Ho, E.; Dashwood, R. H. Histone deacetylase turnover and recovery in sulforaphane-treated colon cancer cells: competing actions of 14-3-3 and Pin1 in HDAC3/SMRT corepressor complex dissociation/reassembly. Mol. Cancer, 2011, 10, 68.
205. Meeran, S. M.; Patel, S. N.; Li, Y.; Shukla, S.; Tollefsbol, T. O. Bioactive dietary supplements reactivate ER expression in ERnegative breast cancer cells by active chromatin modifications. PLoS One, 2012, 7 (5), e37748.
206. Paredes-Gonzalez, X.; Fuentes, F.; Su, Z. Y.; Kong, A. N. Apigenin reactivates Nrf2 anti-oxidative stress signaling in mouse skin epidermal JB6 P + cells through epigenetics modifications. AAPS J., 2014, 16 (4), 727-35.
207. Su, Z. Y.; Zhang, C.; Lee, J. H.; Shu, L.; Wu, T. Y.; Khor, T. O.; Conney, A. H.; Lu, Y. P.; Kong, A. N. Requirement and epigenetics reprogramming of Nrf2 in suppression of tumor promoter TPAinduced mouse skin cell transformation by sulforaphane. Cancer Prev. Res. (Phila.), 2014, 7 (3), 319-29.
208. Lee, S. J.; Krauthauser, C.; Maduskuie, V.; Fawcett, P. T.; Olson, J. M.; Rajasekaran, S. A. Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo. BMC Cancer, 2011, 11, 144.
209. Chen, C. C.; Sureshbabul, M.; Chen, H. W.; Lin, Y. S.; Lee, J. Y.; Hong, Q. S.; Yang, Y. C.; Yu, S. L. Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin Upregulation in Colorectal Cancer. Evid. Based Complement. Alternat. Med., 2013, 2013, 541695.
210. Guo, Y.; Shu, L.; Zhang, C.; Su, Z. Y.; Kong, A. N. Curcumin inhibits anchorage-independent growth of HT29 human colon cancer cells by targeting epigenetic restoration of the tumor suppressor gene DLEC1. Biochem. Pharmacol., 2015, 94 (2), 69-78.
211. Shu, L.; Khor, T. O.; Lee, J. H.; Boyanapalli, S. S.; Huang, Y.; Wu, T. Y.; Saw, C. L.; Cheung, K. L.; Kong, A. N. Epigenetic CpG demethylation of the promoter and reactivation of the expression of Neurog1 by curcumin in prostate LNCaP cells. AAPS J., 2011, 13 (4), 606-14.
212. Thomas, J.; Garg, M. L.; Smith, D. W., Dietary resveratrol supplementation normalizes gene expression in the hippocampus of streptozotocin- induced diabetic C57Bl/6 mice. J. nutr. Biochem., 2014, 25 (3), 313-8.
213. Mirza, S.; Sharma, G.; Parshad, R.; Gupta, S. D.; Pandya, P.; Ralhan, R. Expression of DNA methyltransferases in breast cancer patients and to analyze the effect of natural compounds on DNA methyltransferases and associated proteins. J. Breast Cancer, 2013, 16 (1), 23-31.
214. Qin, W.; Zhang, K.; Clarke, K.; Weiland, T.; Sauter, E. R. Methylation and miRNA effects of resveratrol on mammary tumors vs. normal tissue. Nutr. Cancer, 2014, 66 (2), 270-7.
215. Vaid, M.; Prasad, R.; Singh, T.; Jones, V.; Katiyar, S. K. Grape seed proanthocyanidins reactivate silenced tumor suppressor genes in human skin cancer cells by targeting epigenetic regulators. Toxicol. Appl. Pharmacol., 2012, 263 (1), 122-30.
216. Wang, L. S.; Kuo, C. T.; Cho, S. J.; Seguin, C.; Siddiqui, J.; Stoner, K.; Weng, Y. I.; Huang, T. H.; Tichelaar, J.; Yearsley, M.; Stoner, G. D.; Huang, Y. W. Black raspberry-derived anthocyanins demethylate tumor suppressor genes through the inhibition of DNMT1 and DNMT3B in colon cancer cells. Nutr. Cancer, 2013, 65 (1), 118-25.
217. Nandakumar, V.; Vaid, M.; Katiyar, S. K. (-)-Epigallocatechin-3- gallate reactivates silenced tumor suppressor genes, Cip1/p21 and p16INK4a, by reducing DNA methylation and increasing histones acetylation in human skin cancer cells. Carcinogenesis, 2011, 32 (4), 537-44.
218. Khan, M. A.; Hussain, A.; Sundaram, M. K.; Alalami, U.; Gunasekera, D.; Ramesh, L.; Hamza, A.; Quraishi, U. (-)- Epigallocatechin-3-gallate reverses the expression of various tumor- suppressor genes by inhibiting DNA methyltransferases and histone deacetylases in human cervical cancer cells. Oncol. Rep., 2015, 33 (4), 1976-84.
219. Jiang, S.; Ma, X.; Huang, Y.; Xu, Y.; Zheng, R.; Chiao, J. W. Reactivating aberrantly hypermethylated p15 gene in leukemic T cells by a phenylhexyl isothiocyanate mediated inter-active mechanism on DNA and chromatin. J. Hematol. Oncol., 2010, 3, 48.
220. Hsu, A.; Wong, C. P.; Yu, Z.; Williams, D. E.; Dashwood, R. H.; Ho, E. Promoter de-methylation of cyclin D2 by sulforaphane in prostate cancer cells. Clin. Epigenet., 2011, 3, 3.
221. Zheng, J.; Wu, C.; Lin, Z.; Guo, Y.; Shi, L.; Dong, P.; Lu, Z.; Gao, S.; Liao, Y.; Chen, B.; Yu, F. Curcumin up-regulates phosphatase and tensin homologue deleted on chromosome 10 through microRNA- mediated control of DNA methylation--a novel mechanism suppressing liver fibrosis. FEBS J., 2014, 281 (1), 88-103.
222. Li, H.; Xu, W.; Huang, Y.; Huang, X.; Xu, L.; Lv, Z. Genistein demethylates the promoter of CHD5 and inhibits neuroblastoma growth in vivo. Int. J. Mol. Med., 2012, 30 (5), 1081-6.
223. Crescenti, A.; Sola, R.; Valls, R. M.; Caimari, A.; Del Bas, J. M.; Anguera, A.; Angles, N.; Arola, L. Cocoa Consumption Alters the Global DNA Methylation of Peripheral Leukocytes in Humans with Cardiovascular Disease Risk Factors: A Randomized Controlled Trial. PLoS One, 2013, 8 (6), e65744.
224. Huang, J.; Plass, C.; Gerhauser, C. Cancer chemoprevention by targeting the epigenome. Curr. Drug Targets, 2011, 12 (13), 1925-56.
225. vel Szic, K. S.; Ndlovu, M. N.; Haegeman, G.; Vanden Berghe, W. Nature or nurture: let food be your epigenetic medicine in chronic inflammatory disorders. Biochem. Pharmacol., 2010, 80 (12), 1816-32.
226. Miceli, M.; Bontempo, P.; Nebbioso, A.; Altucci, L. Natural compounds in epigenetics: A current view. Food Chem. Toxicol., 2014, 73, 71-83
227. Martinez, S. R.; Gay, M. S.; Zhang, L. Epigenetic mechanisms in heart development and disease. Drug discov. Today, 2015, 20(7), 799-811
228. Manach, C.; Mazur, A.; Scalbert, A. Polyphenols and prevention of cardiovascular diseases. Curr. Opin. Lipidol., 2005, 16 (1), 77-84.
229. Fisher, N. D.; Hollenberg, N. K. Aging and vascular responses to flavanol-rich cocoa. J. Hypertens., 2006, 24 (8), 1575-80.
230. Sies, H.; Schewe, T.; Heiss, C.; Kelm, M. Cocoa polyphenols and inflammatory mediators. Am. J. Clin. Nutr., 2005, 81 (1 Suppl), 304S-312S.
231. Heiss, C.; Kleinbongard, P.; Dejam, A.; Perre, S.; Schroeter, H.; Sies, H.; Kelm, M. Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers. J. Am. Coll. Cardiol., 2005, 46 (7), 1276-83.
232. Baur, J. A.; Sinclair, D. A. Therapeutic potential of resveratrol: the in vivo evidence. Nat. rev. Drug discov., 2006, 5 (6), 493-506.
233. Bertelli, A. A.; Das, D. K. Grapes, wines, resveratrol, and heart health. J. Cardiovasc. Pharmacol., 2009, 54 (6), 468-76.
234. Chiva-Blanch, G.; Badimon, L.; Estruch, R. Latest evidence of the effects of the mediterranean diet in prevention of cardiovascular disease. Curr. Atheroscler. Rep., 2014, 16 (10), 446.
235. Szarc vel Szic, K.; Declerck, K.; Vidakovic, M.; Vanden Berghe, W. From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics the key to personalized nutrition? Clin. Epigenetics, 2015, 7 (1), 33.
236. Laukkanen, M. O.; Mannermaa, S.; Hiltunen, M. O.; Aittomaki, S.; Airenne, K.; Janne, J.; Yla-Herttuala, S. Local hypomethylation in atherosclerosis found in rabbit ec-sod gene. Arterioscler. Thromb. Vasc. Biol., 1999, 19 (9), 2171-8.