The relevance of epigenetics to occlusive cerebral and peripheral arterial disease

Clinical Science

Volumn 128, Issue 9, 2015, Pages 537-558

  Krishna, Smriti Murali ^a   Trollope, Alexandra Fay ^a   Golledge, Jonathan ^a,b  

^a JAMES COOK UNIVERSITY   (Australia)

^b TOWNSVILLE HOSPITAL   (Australia)

Author keywords

Atherosclerosis; Epigenetics; Ischaemia; Peripheral arterial disease

Indexed keywords

HISTONE H3; HISTONE H4; MICRORNA; OXIDIZED LOW DENSITY LIPOPROTEIN;

ANGIOGENESIS; ATHEROSCLEROSIS; CELL DIFFERENTIATION; CELL PROLIFERATION; CEREBROVASCULAR ACCIDENT; COMORBIDITY; CRITICAL LIMB ISCHEMIA; DNA METHYLATION; ENDOTHELIUM CELL; EPIGENETICS; FIBROBLAST; GENE EXPRESSION REGULATION; HISTONE ACETYLATION; HISTONE MODIFICATION; HISTONE PHOSPHORYLATION; HUMAN; HYPOXIA; INFLAMMATION; NONHUMAN; OCCLUSIVE CEREBROVASCULAR DISEASE; PATIENT SAFETY; PERIPHERAL OCCLUSIVE ARTERY DISEASE; PRIORITY JOURNAL; REVIEW; RISK FACTOR; ANIMAL; CHROMATIN ASSEMBLY AND DISASSEMBLY; DRUG EFFECTS; GENETIC EPIGENESIS; GENETIC PREDISPOSITION; GENETICS; HEMODYNAMICS; INTRACRANIAL ARTERIOSCLEROSIS; METABOLISM; PATHOPHYSIOLOGY; PERIPHERAL ARTERIAL DISEASE; PHENOTYPE;

ANIMALS; CHROMATIN ASSEMBLY AND DISASSEMBLY; DNA METHYLATION; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION; GENETIC PREDISPOSITION TO DISEASE; HEMODYNAMICS; HUMANS; INTRACRANIAL ARTERIOSCLEROSIS; MICRORNAS; PERIPHERAL ARTERIAL DISEASE; PHENOTYPE; RISK FACTORS;

EID: 84927172523     PISSN: 01435221     EISSN: 14708736     Source Type: Journal    
DOI: 10.1042/CS20140491     Document Type: Review

References (208)

1. Norgren, L., Hiatt, W.R., Dormandy, J.A., Nehler, M.R., Harris, K.A., Fowkes, F.G. and Group, T.I.W. (2007) Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J. Vasc. Surg. 45, S5-67
2. Warlow, C., Van Gijn, J., Dennis, M., Wardlaw, J., Bamford, J., Hankey, G., Sandercock, P., Rinkel, G., Langhorne, P., Sudlow, C. and Rothwell, P. (2008) Stroke - Practical Management, 3rd edn. Blackwell Publishing, Victoria, Australia
3. Mackay, J. and Mensah, G. (2004) The global burden of cerebrovascular disease. In The Atlas of Heart Disease and Stroke, 1st edn., World Health Organization, ISBN-10: 9241562765
4. Arnold, T.E. and Kerstein, M.D. (2000) Secondary distal extension of infrainguinal bypass: long-term limb and patient survival. Ann. Vasc. Surg. 14, 450-456
5. Lawall, H., Bramlage, P. and Amann, B. (2011) Treatment of peripheral arterial disease using stem and progenitor cell therapy. J. Vasc. Surg. 53, 445-453
6. Fadini, G.P., Agostini, C. and Avogaro, A. (2010) Autologous stem cell therapy for peripheral arterial disease meta-analysis and systematic review of the literature. Atherosclerosis 209, 10-17
7. Norgren, L., Hiatt, W.R., Dormandy, J.A., Nehler, M.R., Harris, K.A., Fowkes, F.G., Group, T.I.W., Bell, K., Caporusso, J., Durand-Zaleski, I. et al. (2007) Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). Eur. J. Vasc. Endovasc. Surg. 33, 61-75
8. Carmeliet, P. (2000) Mechanisms of angiogenesis and arteriogenesis. Nat. Med. 6 4, 389-395
9. Baccarelli, A. and Ghosh, S. (2012) Environmental exposures, epigenetics and cardiovascular disease. Curr. Opin. Clin. Nutr. Metab. Care 15, 323-329
10. Whayne, T.F. (2014) Epigenetics in the development, modification, and prevention of cardiovascular disease. Mol. Biol. Rep., doi:10.1007/s11033-014-3727-z
11. Allfrey, V.G., Faulkner, R. and Mirsky, A.E. (1964) Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc. Natl. Acad. Sci. U.S.A. 51, 786-794
12. Gurley, L.R., Walters, R.A., Barham, S.S. and Deaven, L.L. (1978) Heterochromatin and histone phosphorylation. Exp. Cell Res. 111, 373-383
13. Ambros, V. (2004) The functions of animal microRNAs. Nature 431, 350-355
14. Mousa, A.A., Cappello, R.E., Estrada-Gutierrez, G., Shukla, J., Romero, R., Strauss, 3rd, J.F. and Walsh, S.W. (2012) Preeclampsia is associated with alterations in DNA methylation of genes involved in collagen metabolism. Am. J. Pathol. 181, 1455-1463
15. Dhar, K., Rakesh, K., Pankajakshan, D. and Agrawal, DK. (2013) SOCS3 promotor hypermethylation and STAT3-NF-κB interaction downregulate SOCS3 expression in human coronary artery smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 304, H776-H785
16. Sorianello, E., Soriano, F.X., Fernández-Pascual, S., Sancho, A., Naon, D., Vila-Caballer, M., González-Navarro, H., Portugal, J., Andrés, V., Palacín, M. and Zorzano, A. (2012) The promoter activity of human Mfn2 depends on Sp1 in vascular smooth muscle cells. Cardiovasc. Res. 94, 38-47
17. Zelko, I.N., Stepp, M.W., Vorst, A.L. and Folz, R.J. (2011) Histone acetylation regulates the cell-specific and interferon-gamma-inducible expression of extracellular superoxide dismutase in human pulmonary arteries. Am. J. Respir. Cell Mol. Biol. 45, 953-961
18. Li, L., Xie, J., Zhang, M. and Wang, S. (2009) Homocysteine harasses the imprinting expression of IGF2 and H19 by demethylation of differentially methylated region between IGF2/H19 genes. Acta Biochim. Biophys. Sin. 41, 464-471
19. Dunn, J., Qiu, H., Kim, S., Jjingo, D., Hoffman, R., Kim, C.W., Jang, I., Son, D.J., Kim, D., Pan, C. et al. (2014) Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosis. J. Clin. Invest. 124, 3187-3199
20. Quentmeier, H., Eberth, S., Romani, J., Weich, H.A., Zaborski, M. and Drexler, H.G. (2012) DNA methylation regulates expression of VEGF-R2 (KDR) and VEGF-R3 (FLT4). BMC Cancer 12, 19
21. Zhang, D., Chen, Y., Xie, X., Liu, J., Wang, Q., Kong, W. and Zhu, Y. (2012) Homocysteine activates vascular smooth muscle cells by DNA demethylation of platelet-derived growth factor in endothelial cells. J. Mol. Cell. Cardiol. 53, 487-496
22. Zhang, B.K., Lai, Y.Q., Niu, P.P., Zhao, M. and Jia, S.J. (2013) Epigallocatechin-3-gallate inhibits homocysteine-induced apoptosis of endothelial cells by demethylation of the DDAH2 gene. Planta Med. 79, 1715-1719
23. Fish, J.E., Matouk, C.C., Rachlis, A., Lin, S., Tai, S.C., D'Abreo, C. and Marsden, P.A. (2005) The expression of endothelial nitric-oxide synthase is controlled by a cell-specific histone code. J. Biol. Chem. 280, 24824-24838
24. Rao, X., Zhong, J., Zhang, S., Zhang, Y., Yu, Q., Yang, P., Wang, M.H., Fulton, D.J., Shi, H., Dong, Z. et al. (2011) Loss of methyl-CpG-binding domain protein 2 enhances endothelial angiogenesis and protects mice against hind-limb ischemic injury. Circulation 123, 2964-2974
25. Robinson, C.M., Neary, R., Levendale, A., Watson, C.J. and Baugh, J.A. (2012) Hypoxia-induced DNA hypermethylation in human pulmonary fibroblasts is associated with Thy-1 promoter methylation and the development of a pro-fibrotic phenotype. Respir. Res. 13, 74
26. Hu, B., Gharaee-Kermani, M.M., Wu, Z. and Phan, S.H. (2011) Essential role of MeCP2 in the regulation of myofibroblast differentiation during pulmonary fibrosis. Am. J. Pathol. 178, 1500-1508
27. Hu, B, Gharaee-Kermani, M.M., Wu, Z. and Phan, S.H. (2010) Epigenetic regulation of myofibroblast differentiation by DNA methylation. Am. J. Pathol. 177, 21-28
28. Klein, D., Benchellal, M., Kleff, V., Jakob, H.G. and Ergün, S. (2013) Hox genes are involved in vascular wall-resident multipotent stem cell differentiation into smooth muscle cells. Sci. Rep. 2178, 3
29. Hu, C.J., Chen, S., Yang, D.I., Lin, T.N., Chen, C.M., Huang, T.H. and Hsu, C.Y. (2006) Promoter region methylation and reduced expression of thrombospondin-1 after oxygen-glucose deprivation in murine cerebral endothelial cells. J. Cereb. Blood Flow Metab. 26, 1519-1526
30. Montes de Oca, A., Madueno, J.A., Martinez-Moreno, J.M., Guerrero, F., Munoz-Castaneda, J., Rodriguez-Ortiz, M.E., Mendoza, F.J., Almaden, Y., Lopez, I., Rodriguez, M. and Aguilera-Tejero, E. (2010) High-phosphate-induced calcification is related to SM22alpha promoter methylation in vascular smooth muscle cells. J. Bone Miner. Res. 25, 1996-2005
31. Siuda, D., Zechner, U., El Hajj, N., Prawitt, D., Langer, D., Xia, N., Horke, S., Pautz, A., Kleinert, H., Förstermann, U. and Li, H. (2012) Transcriptional regulation of Nox4 by histone deacetylases in human endothelial cells. Basic Res. Cardiol. 107, 283
32. Kumar, A., Kumar, S., Vikram, A., Hoffman, T.A., Naqvi, A., Lewarchik, C.M., Kim, Y.R. and Irani, K. (2013) Histone and DNA methylation-mediated epigenetic downregulation of endothelial Kruppel-like factor 2 by low-density lipoprotein cholesterol. Arterioscler. Thromb. Vasc. Biol. 33, 1936-1942
33. Gomez, D., Coyet, A., Ollivier, V., Jeunemaitre, X., Jondeau, G., Michel, J.B. and Vranckx, R. (2011) Epigenetic control of vascular smooth muscle cells in Marfan and non-Marfan thoracic aortic aneurysms. Cardiovasc Res. 89, 446-456
34. Seo, J., Kim, Y.O. and Jo, I. (2009) Differential expression of stromal cell-derived factor 1 in human brain microvascular endothelial cells and pericytes involves histone modifications. Biochem. Biophys. Res. Commun. 382, 519-524
35. Harris, T.A., Yamakuchi, M., Ferlito, M., Mendell, J.T. and Lowenstein, C.J. (2008) MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc. Natl. Acad. Sci. U.S.A. 105, 1516-1521
36. Zhu, N., Zhang, D., Chen, S., Liu, X., Lin, L., Huang, X., Guo, Z., Liu, J., Wang, Y., Yuan, W. and Qin, Y. (2011) Endothelial enriched microRNAs regulate angiotensin II-induced endothelial inflammation and migration. Atherosclerosis 215, 286-293
37. Kuehbacher, A., Urbich, C., Zeiher, A.M. and Dimmeler, S. (2007) Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circ. Res. 101, 59-68
38. Fasanaro, P., D'Alessandra, Y., Di Stefano, V., Melchionna, R., Romani, S., Pompilio, G., Capogrossi, M.C. and Martelli, F. (2008) MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J. Biol. Chem. 283, 15878-15883
39. Chen, K.C., Wang, Y., Hu, C.Y., Chang, W.C., Liao, Y.C., Dai, C.Y. and Juo, S.H. (2011) OxLDL up-regulates microRNA-29b, leading to epigenetic modifications of MMP-2/MMP-9 genes: a novel mechanism for cardiovascular diseases. FASEB J. 25, 1718-1728
40. Bird, A. (2002) DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6-21
41. Tahiliani, M., Koh, K.P., Shen, Y., Pastor, W.A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L.M., Liu, D.R., Aravind, L. and Rao, A. (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324, 930-935
42. Ramchandani, S, Bhattacharya, S., Cervoni, N. and Szyf, M. (1999) DNA methylation is a reversible biological signal. Proc. Natl. Acad. Sci. U.S.A. 96, 6107-6112
43. Eom, G.H. and Kook, H. (2014) Posttranslational modifications of histone deacetylases: implications for cardiovascular diseases. Pharmacol. Ther. 143, 168-180
44. Jenuwein, T. and Allis, C.D. (2001) Translating the histone code. Science 293, 1074-1080
45. Pons, D., de Vries, F.R., van den Elsen, P.J., Heijmans, B.T., Quax, P.H. and Jukema, J.W. (2009) Epigenetic histone acetylation modifiers in vascular remodelling: new targets for therapy in cardiovascular disease. Eur. Heart J. 30, 266-277
46. Santos-Rosa, H., Schneider, R., Bannister, A.J., Sherriff, J., Bernstein, B.E., Emre, N.C., Schreiber, S.L., Mellor, J. and Kouzarides, T. (2002) Active genes are tri-methylated at K4 of histone H3. Nature 419, 407-411
47. Mathiyalagan, P., Chang, L., Du, X.J. and El-Osta, A. (2010) Cardiac ventricular chambers are epigenetically distinguishable. Cell Cycle 9, 612-617
48. Villeneuve, L., Reddy, M.A., Lanting, L.L., Wang, M., Meng, L. and Natarajan, R. (2008) Epigenetic histone H3 lysine 9 methylation in metabolic memory and inflammatory phenotype of vascular smooth muscle cells in diabetes. Proc. Natl. Acad. Sci. U.S.A. 105, 9047-9052
49. Winter, J., Jung, S., Keller, S., Gregory, R.I. and Diederichs, S. (2009) Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat. Cell Biol. 11, 228-234
50. Lewis, B.P., Burge, C.B. and Bartel, D.P. (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15-20
51. Guo, H., Ingolia, N.T., Weissman, J.S. and Bartel, D.P. (2010) Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466, 835-840
52. Place, R.F., Li, L.C., Pookot, D., Noonan, E.J. and Dahiya, R. (2008) MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc. Natl. Acad. Sci. U.S.A. 105, 1608-1613
53. Kim, D.H., Saetrom, P., Snove, Jr, O. and Rossi, J.J. (2008) MicroRNA-directed transcriptional gene silencing in mammalian cells. Proc. Natl. Acad. Sci. U.S.A. 105, 16230-16235
54. Marinova, Z., Ren, M., Wendland, J.R., Leng, Y., Liang, M.H., Yasuda, S., Leeds, P. and Chuang, D.M. (2009) Valproic acid induces functional heat-shock protein 70 via Class I histone deacetylase inhibition in cortical neurons: a potential role of Sp1 acetylation. J. Neurochem. 111, 976-987
55. Marinova, Z., Leng, Y., Leeds, P. and Chuang, D.M. (2011) Histone deacetylase inhibition alters histone methylation associated with heat shock protein 70 promoter modifications in astrocytes and neurons. Neuropharmacology 60, 1109-1115
56. Hunsberger, J.G., Fessler, E., Wang, Z., Elkahloun, A.G. and Chuang, D.M. (2012) Post-insult valproic acid-regulated microRNAs: potential targets for cerebral ischemia. Am. J. Transl. Res. 4, 316-332
57. Amir, R.E., Van den Veyver, I.B., Wan, M., Tran, C.Q., Francke, U. and Zoghbi, H.Y. (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23, 185-188
58. Chen, L.J., Wei, S.Y. and Chiu, J.J. (2013) Mechanical regulation of epigenetics in vascular biology and pathobiology. J. Cell Mol. Med. 17, 437-448
59. Choi, J.H., Nam, K.H., Kim, J., Baek, M.W., Park, J.E., Park, H.Y., Kwon, H.J., Kwon, O.S., Kim, D.Y. and Oh, G.T. (2005) Trichostatin A exacerbates atherosclerosis in low density lipoprotein receptor-deficient mice. Arterioscler Thromb. Vasc. Biol. 25, 2404-2409
60. Okamoto, H., Fujioka, Y., Takahashi, A., Takahashi, T., Taniguchi, T., Ishikawa, Y. and Yokoyama, M. (2006) Trichostatin A, an inhibitor of histone deacetylase, inhibits smooth muscle cell proliferation via induction of p21(WAF1). J. Atheroscler. Thromb. 13, 183-191
61. Dje N'Guessan, P., Riediger, F., Vardarova, K., Scharf, S., Eitel, J., Opitz, B., Slevogt, H., Weichert, W., Hocke, A.C., Schmeck, B. et al. (2009) Statins control oxidized LDL-mediated histone modifications and gene expression in cultured human endothelial cells. Arterioscler. Thromb. Vasc. Biol. 29, 380-386
62. Jiang, Y.Z., Jimenez, J.M., Ou, K., McCormick, M.E., Zhang, L.D. and Davies, P.F. (2014) Hemodynamic disturbed flow induces differential DNA methylation of endothelial kruppel-like factor 4 promoter in vitro and in vivo. Circ. Res. 115, 32-43
63. Hastings, N.E., Simmers, M.B., McDonald, O.G., Wamhoff, B.R. and Blackman, B.R. (2007) Atherosclerosis-prone hemodynamics differentially regulates endothelial and smooth muscle cell phenotypes and promotes pro-inflammatory priming. Am. J. Physiol. Cell Physiol. 293, C1824-C1833
64. Fan, J., Alsarraf, O., Dahrouj, M., Platt, K.A., Chou, C.J., Rice, D.S. and Crosson, C.E. (2013) Inhibition of HDAC2 protects the retina from ischemic injury. Invest. Ophthalmol. Vis. Sci. 54, 4072-4080
65. Wellmann, S., Bettkober, M., Zelmer, A., Seeger, K., Faigle, M., Eltzschig, H.K. and Buhrer, C. (2008) Hypoxia upregulates the histone demethylase JMJD1A via HIF-1. Biochem. Biophys. Res. Commun. 372, 892-897
66. Pollard, P.J., Loenarz, C., Mole, D.R., McDonough, M.A., Gleadle, J.M., Schofield, C.J. and Ratcliffe, P.J. (2008) Regulation of Jumonji-domain-containing histone demethylases by hypoxia-inducible factor (HIF)-1alpha. Biochem. J. 416, 387-394
67. Saco, T.V., Parthasarathy, P.T., Cho, Y., Lockey, R.F. and Kolliputi, N. (2014) Role of epigenetics in pulmonary hypertension. Am. J. Physiol. Cell Physiol. 306, C1101-C1105
68. Chen, W., Bacanamwo, M. and Harrison, D.G. (2008) Activation of p300 histone acetyltransferase activity is an early endothelial response to laminar shear stress and is essential for stimulation of endothelial nitric-oxide synthase mRNA transcription. J. Biol. Chem. 283, 16293-16298
69. Zhang, L., Qin, X., Zhao, Y., Fast, L., Zhuang, S., Liu, P., Cheng, G. and Zhao, T.C. (2012) Inhibition of histone deacetylases preserves myocardial performance and prevents cardiac remodeling through stimulation of endogenous angiomyogenesis. J. Pharmacol. Exp. Ther. 341, 285-293
70. Semenza, G.L. (2000) Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit. Rev. Biochem. Mol. Biol. 35, 71-103
71. Kim, M.S., Kwon, H.J., Lee, Y.M., Baek, J.H., Jang, J.E., Lee, S.W., Moon, E.J., Kim, H.S., Lee, S.K., Chung, H.Y. et al. (2001) Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nat. Med. 7, 437-443
72. Chen, S. and Sang, N. (2011) Histone deacetylase inhibitors: the epigenetic therapeutics that repress hypoxia-inducible factors. J. Biomed. Biotechnol. 2011, 197946
73. Johnson, A.B., Denko, N. and Barton, M.C. (2008) Hypoxia induces a novel signature of chromatin modifications and global repression of transcription. Mutat. Res. 640, 174-179
74. Chen, H., Yan, Y., Davidson, T.L., Shinkai, Y. and Costa, M. (2006) Hypoxic stress induces dimethylated histone H3 lysine 9 through histone methyltransferase G9a in mammalian cells. Cancer Res. 66, 9009-9016.
75. Lee, S.H., Kim, J., Kim, W.H. and Lee, Y.M. (2009) Hypoxic silencing of tumor suppressor RUNX3 by histone modification in gastric cancer cells. Oncogene 28, 184-194
76. Beyer, S., Kristensen, M.M., Jensen, K.S., Johansen, J.V. and Staller, P. (2008) The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF. J. Biol. Chem. 283, 36542-36552
77. Yang, J., Ledaki, I., Turley, H., Gatter, K.C., Montero, J.C., Li, J.L. and Harris, A.L. (2009) Role of hypoxia-inducible factors in epigenetic regulation via histone demethylases. Ann. N. Y. Acad. Sci. 1177, 185-197
78. Krieg, A.J., Rankin, E.B., Chan, D., Razorenova, O., Fernandez, S. and Giaccia, A.J. (2010) Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth. Mol. Cell. Biol. 30, 344-353
79. Glazer, P.M., Hegan, D.C., Lu, Y., Czochor, J. and Scanlon, S.E. (2013) Hypoxia and DNA repair. Yale J. Biol. Med. 86, 443-451
80. Lu, Y., Chu, A., Turker, M.S. and Glazer, P.M. (2011) Hypoxia-induced epigenetic regulation and silencing of the BRCA1 promoter. Mol. Cell. Biol. 31, 3339-3350
81. Tudisco, L., Della Ragione, F., Tarallo, V., Apicella, I., D'Esposito, M., Matarazzo, M.R. and De Falco, S. (2014) Epigenetic control of hypoxia inducible factor-1alpha-dependent expression of placental growth factor in hypoxic conditions. Epigenetics 9, 600-610
82. Chen, D., Fang, F., Yang, Y., Chen, J., Xu, G., Xu, Y. and Gao, Y. (2013) Brahma-related gene 1 (Brg1) epigenetically regulates CAM activation during hypoxic pulmonary hypertension. Cardiovasc. Res. 100, 363-373
83. Fang, F., Chen, D., Yu, L., Dai, X., Yang, Y., Tian, W., Cheng, X., Xu, H., Weng, X., Fang, M. et al. (2013) Proinflammatory stimuli engage Brahma related gene 1 and Brahma in endothelial injury. Circ. Res. 113, 986-996
84. Wu, X., Chen, P.S., Dallas, S., Wilson, B., Block, M.L., Wang, C.C., Kinyamu, H., Lu, N., Gao, X., Leng, Y. et al. (2008) Histone deacetylase inhibitors up-regulate astrocyte GDNF and BDNF gene transcription and protect dopaminergic neurons. Int. J. Neuropsychopharmacol. 11, 123-134
85. Yoshida, M., Kijima, M., Akita, M. and Beppu, T. (1990) Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J. Biol. Chem. 265, 17174-17179
86. Langley, B., D'Annibale, M.A., Suh, K., Ayoub, I., Tolhurst, A., Bastan, B., Yang, L., Ko, B., Fisher, M., Cho, S. et al. (2008) Pulse inhibition of histone deacetylases induces complete resistance to oxidative death in cortical neurons without toxicity and reveals a role for cytoplasmic p21(waf1/cip1) in cell cycle-independent neuroprotection. J. Neurosci. 28, 163-176
87. Wang, B., Zhu, X., Kim, Y., Li, J., Huang, S., Saleem, S., Li, R.C., Xu, Y., Dore, S. and Cao, W. (2012) Histone deacetylase inhibition activates transcription factor Nrf2 and protects against cerebral ischemic damage. Free Radic. Biol. Med. 52, 928-936
88. Okamoto, H., Fujioka, Y., Takahashi, A., Takahashi, T., Taniguchi, T., Ishikawa, Y. and Yokoyama, M. (2006) Trichostatin A, an inhibitor of histone deacetylase, inhibits smooth muscle cell proliferation via induction of p21(WAF1). J. Atheroscler. Thromb. 13, 183-191
89. Fleiss, B., Nilsson, M.K., Blomgren, K. and Mallard, C. (2012) Neuroprotection by the histone deacetylase inhibitor trichostatin A in a model of lipopolysaccharide-sensitised neonatal hypoxic-ischaemic brain injury. J. Neuroinflamm. 9, 2094-2070
90. Hsieh, J., Nakashima, K., Kuwabara, T., Mejia, E. and Gage, F.H. (2004) Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells. Proc. Natl. Acad. Sci. U.S.A. 101, 16659-16664
91. Gul, H., Marquez-Curtis, L.A., Jahroudi, N., Lo, J., Turner, A.R. and Janowska-Wieczorek, A. (2009) Valproic acid increases CXCR4 expression in hematopoietic stem/progenitor cells by chromatin remodeling. Stem. Cell Dev. 18, 831-838
92. Sinn, D.I., Kim, S.J., Chu, K., Jung, K.H., Lee, S.T., Song, E.C., Kim, J.M., Park, D.K., Kun Lee, S., Kim, M. and Roh, J.K. (2007) Valproic acid-mediated neuroprotection in intracerebral hemorrhage via histone deacetylase inhibition and transcriptional activation. Neurobiol. Dis. 26, 262-272
93. Ren, M., Leng, Y., Jeong, M., Leeds, P.R. and Chuang, D.M. (2004) Valproic acid reduces brain damage induced by transient focal cerebral ischemia in rats: potential roles of histone deacetylase inhibition and heat shock protein induction. J. Neurochem. 89, 1358-1367
94. Wang, Z., Leng, Y., Tsai, L.K., Leeds, P. and Chuang, D.M. (2011) Valproic acid attenuates blood-brain barrier disruption in a rat model of transient focal cerebral ischemia: the roles of HDAC and MMP-9 inhibition. J. Cereb. Blood Flow Metab. 31, 52-57
95. Wang, Z., Tsai, L., Munasinghe, J., Leng, Y., Fessler, E.B., Chibane, F., Leeds, P. and Chuang, D.M. (2012) Chronic valproate treatment enhances postischemic angiogenesis and promotes functional recovery in a rat model of ischemic stroke. Stroke 43, 2430-2436
96. Faraco, G., Pancani, T., Formentini, L., Mascagni, P., Fossati, G., Leoni, F., Moroni, F. and Chiarugi, A. (2006) Pharmacological inhibition of histone deacetylases by suberoylanilide hydroxamic acid specifically alters gene expression and reduces ischemic injury in the mouse brain. Mol. Pharmacol. 70, 1876-1884
97. Faraco, G., Pittelli, M., Cavone, L., Fossati, S., Porcu, M., Mascagni, P., Fossati, G., Moroni, F. and Chiarugi, A. (2009) Histone deacetylase (HDAC) inhibitors reduce the glial inflammatory response in vitro and in vivo. Neurobiol. Dis. 36, 269-729
98. Kim, H., Leeds, P. and Chuang, D.M. (2009) The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain. J. Neurochem. 110, 1226-1240
99. Rubenstein, R.C. and Zeitlin, P.L. (1998) A pilot clinical trial of oral sodium 4-phenylbutyrate (Buphenyl) in deltaF508-homozygous cystic fibrosis patients: partial restoration of nasal epithelial CFTR function. Am. J. Respir. Crit. Med. 157, 484-490
100. Qi, X., Hosoi, T., Okuma, Y., Kaneko, M. and Nomura, Y. (2004) Sodium 4-phenylbutyrate protects against cerebral ischemic injury. Mol. Pharmacol. 66, 899-908
101. Jin, G., Bausch, D., Knightly, T., Liu, Z., Li, Y., Liu, B., Lu, J., Chong, W., Velmahos, G.C. and Alam, H.B. (2011) Histone deacetylase inhibitors enhance endothelial cell sprouting angiogenesis in vitro. Surgery 150, 429-435
102. Kwon, H.J., Kim, M., Kim, M.J., Nakajima, H. and Kim, K.W. (2002) Histone deacetylase inhibitor FK228 inhibits tumor angiogenesis. Int. J. Cancer. 97, 290-296
103. Piekarz, R.L., Robey, R., Sandor, V., Bakke, S., Wilson, W.H., Dahmoush, L., Kingma, D.M., Turner, M.L., Altemus, R. and Bates, S.E. (2001) Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T-cell lymphoma: a case report. Blood. 98, 2865-2868
104. Kogure, K. and Kato, H. (1993) Altered gene expression in cerebral ischemia. Stroke 24, 2121-2127
105. Endres, M., Meisel, A., Biniszkiewicz, D., Namura, S., Prass, K., Ruscher, K., Lipski, A., Jaenisch, R., Moskowitz, M. A. and Dirnagl, U. (2000) DNA methyltransferase contributes to delayed ischemic brain injury. J. Neurosci. 20, 3175-3181
106. Endres, M., Fan, G., Meisel, A., Dirnagl, U. and Jaenisch, R. (2001) Effects of cerebral ischemia in mice lacking DNA methyltransferase 1 in post-mitotic neurons. Neuroreport 12, 3763-3766
107. Liu, P.K., Hsu, C.Y., Dizdaroglu, M., Floyd, R.A., Kow, Y.W., Karakaya, A., Rabow, L.E. and Cui, J.K. (1996) Damage, repair, and mutagenesis in nuclear genes after mouse forebrain ischemia-reperfusion. J. Neurosci. 16, 6795-6805
108. Giffard, R. and Yenari, M.A. (2004) Many mechanisms for hsp70 protection from cerebral ischemia. J. Neurosurg. Anesthesiol. 16, 53-61
109. Kim, A.K., Kim, M.H., Kim, S., Oh, W., Hong, H.K., Kang, K.S., Kim, B.S. and Kim, D.I. (2011) Stem-cell therapy for peripheral arterial occlusive disease. Eur. J. Vasc. Endovasc. Surg. 42, 667-675
110. Sica, V., Williams-Ignarro, S., de Nigris, F., D'Armiento, F.P., Lerman, L.O., Balestrieri, M.L., Maione, C., Palagiano, A., Rossiello, L., Ignarro, L.J. and Napoli, C. (2006) Autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the diabetic mouse hindlimb. Cell Cycle. 5, 2903-2908
111. Hellingman, A.A., Zwaginga, J.J., van Beem, R.T., Te, R. M. S. M. C., Hamming, J.F., Fibbe, W.E., Quax, P.H. and Geutskens, S.B. (2011) T-cell-pre-stimulated monocytes promote neovascularisation in a murine hind limb ischaemia model. Eur. J. Vasc. Endovasc. Surg. 41, 418-428
112. Turunen, M.P., Lehtola, T., Heinonen, S.E., Assefa, G.S., Korpisalo, P., Girnary, R., Glass, C.K., Vaisanen, S. and Yla-Herttuala, S. (2009) Efficient regulation of VEGF expression by promoter-targeted lentiviral shRNAs based on epigenetic mechanism: a novel example of epigenetherapy. Circ. Res. 105, 604-609
113. Palii, C.G., Vulesevic, B., Fraineau, S., Pranckeviciene, E., Griffith, A.J., Chu, A., Faralli, H., Li, Y., McNeill, B., Sun, J. et al. (2014) Trichostatin A enhances vascular repair by injected human endothelial progenitors through increasing the expression of TAL1-dependent genes. Cell Stem Cell 14, 644-657
114. Ueda, H., Matsunaga, H. and Halder, S.K. (2012) Prothymosin alpha plays multifunctional cell robustness roles in genomic, epigenetic, and nongenomic mechanisms. Ann. N. Y. Acad. Sci. 1269, 34-43
115. Spallotta, F., Tardivo, S., Nanni, S., Rosati, J.D., Straino, S., Mai, A., Vecellio, M., Valente, S., Capogrossi, M.C., Farsetti, A. et al. (2013) Detrimental effect of class-selective histone deacetylase inhibitors during tissue regeneration following hindlimb ischemia. J. Biol. Chem. 288, 22915-22929
116. Rahmatzadeh, M., Liu, H.B., Krishna, S.M., Gaspari, T.A., Welungoda, I., Widdop, R.E. and Dear, A.E. (2014) A novel agent with histone deacetylase inhibitory activity attenuates neointimal hyperplasia. Cardiovasc. Drugs Ther. 28, 395-406
117. Chen, S., Feng, B., George, B., Chakrabarti, R., Chen, M. and Chakrabarti, S. (2010) Transcriptional coactivator p300 regulates glucose-induced gene expression in endothelial cells. Am. J. Physiol. Endocrinol Metab. 298, E127-137
118. Zhong, Q. and Kowluru, R.A. (2010) Role of histone acetylation in the development of diabetic retinopathy and the metabolic memory phenomenon. J. Cell. Biochem. 110, 1306-1313
119. Kovacs, B., Lumayag, S., Cowan, C. and Xu, S. (2011) MicroRNAs in early diabetic retinopathy in streptozotocin-induced diabetic rats. Invest. Ophthalmol Vis. Sci. 52, 4402-4409
120. Noh, H., Oh, E.Y., Seo, J.Y., Yu, M.R., Kim, Y.O., Ha, H. and Lee, H.B. (2009) Histone deacetylase-2 is a key regulator of diabetes- and transforming growth factor-beta1-induced renal injury. Am. J. Physiol. Renal. Physiol. 297, F729-F739
121. McArthur, K., Feng, B., Wu, Y., Chen, S. and Chakrabarti, S. (2011) MicroRNA-200b regulates vascular endothelial growth factor-mediated alterations in diabetic retinopathy. Diabetes 60, 1314-1323
122. Zhang, D., Yu, Z.Y., Cruz, P., Kong, Q., Li, S. and Kone, B.C. (2009) Epigenetics and the control of epithelial sodium channel expression in collecting duct. Kidney Int. 75, 260-267
123. Smolarek, I., Wyszko, E., Barciszewska, A.M., Nowak, S., Gawronska, I., Jablecka, A. and Barciszewska, M.Z. (2010) Global DNA methylation changes in blood of patients with essential hypertension. Med. Sci. Monit. 16, CR149-155
124. Lee, M.E. and Wang, H. (1999) Homocysteine and hypomethylation. A novel link to vascular disease. Trends Cardiovasc Med. 9, 49-54
125. Yan, T.T., Li, Q., Zhang, X.H., Wu, W.K., Sun, J., Li, L., Zhang, Q. and Tan, H.M. (2010) Homocysteine impaired endothelial function through compromised vascular endothelial growth factor/Akt/endothelial nitric oxide synthase signalling. Clin. Exp. Pharmacol. Physiol. 37, 1071-1077
126. Dayal, S., Bottiglieri, T., Arning, E., Maeda, N., Malinow, M.R., Sigmund, C.D., Heistad, D.D., Faraci, F.M. and Lentz, S.R. (2001) Endothelial dysfunction and elevation of S-adenosylhomocysteine in cystathionine beta-synthase-deficient mice. Circ. Res. 88, 1203-1209
127. Ying, A.K., Hassanain, H.H., Roos, C.M., Smiraglia, D.J., Issa, J.J., Michler, R.E., Caligiuri, M., Plass, C. and Goldschmidt-Clermont, P.J. (2000) Methylation of the estrogen receptor-alpha gene promoter is selectively increased in proliferating human aortic smooth muscle cells. Cardiovasc Res. 46, 172-179
128. Magenta, A., Cencioni, C., Fasanaro, P., Zaccagnini, G., Greco, S., Sarra-Ferraris, G., Antonini, A., Martelli, F. and Capogrossi, M.C. (2011) miR-200c is upregulated by oxidative stress and induces endothelial cell apoptosis and senescence via ZEB1 inhibition. Cell Death Differ. 18, 1628-1639
129. Bhaumik, D., Scott, G.K., Schokrpur, S., Patil, C.K., Orjalo, A.V., Rodier, F., Lithgow, G.J. and Campisi, J. (2009) MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8. Aging. 1, 402-411
130. Ito, T., Yagi, S. and Yamakuchi, M. (2010) MicroRNA-34a regulation of endothelial senescence. Biochem. Biophys. Res. Commun. 398, 735-740
131. Menghini, R., Casagrande, V., Cardellini, M., Martelli, E., Terrinoni, A., Amati, F., Vasa-Nicotera, M., Ippoliti, A., Novelli, G., Melino, G. et al. (2009) MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1. Circulation 120, 1524-1532
132. Breitling, L.P., Yang, R., Korn, B., Burwinkel, B. and Brenner, H. (2011) Tobacco-smoking-related differential DNA methylation: 27K discovery and replication. Am. J. Hum. Genet. 88, 450-457
133. Zöchbauer-Müller, S., Lam, S., Toyooka, S., Virmani, A.K., Toyooka, K.O., Seidl, S., Minna, J.D. and Gazdar, A.F. (2003) Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers. Int. J. Cancer 107, 612-616
134. Yanagawa, N., Tamura, G., Oizumi, H., Endoh, M., Sadahiro, M. and Motoyama, T. (2011) Inverse correlation between EGFR mutation and FHIT, RASSF1A and RUNX3 methylation in lung adenocarcinoma: relation with smoking status. Anticancer Res. 31, 1211-1214
135. Ostrow, K.L., Hoque, M.O., Loyo, M., Brait, M., Greenberg, A., Siegfried, J.M., Grandis, J.R., Gaither Davis, A., Bigbee, W.L., Rom, W. and Sidransky, D. (2010) Molecular analysis of plasma DNA for the early detection of lung cancer by quantitative methylation-specific PCR. Clin. Cancer Res. 16, 3463-3472
136. Breton, C.V., Byun, H.M., Wenten, M., Pan, F., Yang, A. and Gilliland, F.D. (2009) Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. Am. J. Respir. Crit. Care Med. 180, 462-467
137. Sharma, P., Kumar, J., Garg, G., Kumar, A., Patowary, A., Karthikeyan, G., Ramakrishnan, L., Brahmachari, V. and Sengupta, S. (2008) Detection of altered global DNA methylation in coronary artery disease patients. DNA Cell. Biol. 27, 357-365
138. Pearce, M.S., McConnell, J.C., Potter, C., Barrett, L.M., Parker, L., Mathers, J.C. and Relton, C.L. (2012) Global LINE-1 DNA methylation is associated with blood glycaemic and lipid profiles. Int. J. Epidemiol 41, 210-217
139. Kawano, N., Emoto, M., Mori, K., Yamazaki, Y., Urata, H., Tsuchikura, S., Motoyama, K., Morioka, T., Fukumoto, S., Shoji, T. et al. (2012) Association of endothelial and vascular smooth muscle dysfunction with cardiovascular risk factors, vascular complications, and subclinical carotid atherosclerosis in type 2 diabetic patients. J. Atheroscler. Thromb. 19, 276-284
140. Villeneuve, L.M. and Natarajan, R. (2010) The role of epigenetics in the pathology of diabetic complications. Am. J. Physiol. Renal. Physiol. 299, F14-F25
141. Krishna, S.M., Dear, A., Craig, J.M., Norman, P.E. and Golledge, J. (2013) The potential role of homocysteine mediated DNA methylation and associated epigenetic changes in abdominal aortic aneurysm formation. Atherosclerosis 228, 295-305
142. Becker, A., Kostense, P.J., Bos, G., Heine, R.J., Dekker, J.M., Nijpels, G., Bouter, L.M. and Stehouwer, C.D. (2003) Hyperhomocysteinaemia is associated with coronary events in type 2 diabetes. J. Intern. Med. 253, 293-300
143. Okura, T., Miyoshi, K., Irita, J., Enomoto, D., Nagao, T., Kukida, M., Tanino, A., Kudo, K., Pei, Z. and Higaki, J. (2014) Hyperhomocysteinemia is one of the risk factors associated with cerebrovascular stiffness in hypertensive patients, especially elderly males. Sci. Rep. 4, 5663
144. Heneghan, H.M. and Sultan, S. (2008) Homocysteine, the cholesterol of the 21st century. Impact of hyperhomocysteinemia on patency and amputation-free survival after intervention for critical limb ischemia. J. Endovasc. Ther. 15, 399-407
145. Talaulikar, V.S. and Arulkumaran, S. (2011) Folic acid in obstetric practice: a review. Obstet. Gynecol. Surv. 66, 240-247
146. Jiang, X., Yang, F., Tan, H., Liao, D., Bryan, Jr, R. M., Randhawa, J.K., Rumbaut, R.E., Durante, W., Schafer, A.I., Yang, X. and Wang, H. (2005) Hyperhomocystinemia impairs endothelial function and eNOS activity via PKC activation. Arterioscler. Thromb. Vasc. Biol. 25, 2515-2521
147. De Smet, C., Lurquin, C., Lethe, B., Martelange, V. and Boon, T. (1999) DNA methylation is the primary silencing mechanism for a set of germ line- and tumor-specific genes with a CpG-rich promoter. Mol. Cell. Biol. 19, 7327-7335
148. Kruman, I.I., Culmsee, C., Chan, S.L., Kruman, Y., Guo, Z., Penix, L. and Mattson, M.P. (2000) Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J. Neurosci. 20, 6920-6926
149. Werstuck, G.H., Lentz, S.R., Dayal, S., Hossain, G.S., Sood, S.K., Shi, Y.Y., Zhou, J., Maeda, N., Krisans, S.K., Malinow, M.R. and Austin, R.C. (2001) Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways. J. Clin. Invest. 107, 1263-1273
150. Savji, N., Rockman, C., Skolnick, A.H., Guo, Y., Adelman, M.A., Riles, T. and Berger, J.S. (2013) Association between advanced age and vascular disease in different arterial territories: a population database of over 3.6 million subjects. J. Am. Coll. Cardiol. 61, 1736-1743
151. Bjornsson, H.T., Sigurdsson, M., Fallin, M.D., Irizarry, R.A., Aspelund, T., Cui, H., Yu, W., Rongione, M.A., Ekström, T.J., Harris, T.B. et al. (2008) Intra-individual change over time in DNA methylation with familial clustering. JAMA 299, 2877-2883
152. Rupérez, M., Lorenzo, O., Blanco-Colio, L.M., Esteban, V., Egido, J. and Ruiz-Ortega, M. (2003) Connective tissue growth factor is a mediator of angiotensin II-induced fibrosis. Circulation 108, 1499-1505
153. Yu, Z., Kong, Q. and Kone, B.C. (2010) CREB trans-activation of disruptor of telomeric silencing-1 mediates forskolin inhibition of CTGF transcription in mesangial cells. Am. J. Physiol. Renal Physiol. 298, F617-F624
154. Lipson, K., Wong, C., Teng, Y. and Spong, S. (2012) CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis. Fibrogenesis Tissue Repair 5, S24
155. Begum, S., Brait, M., Dasgupta, S., Ostrow, K.L., Zahurak, M., Carvalho, A.L., Califano, J.A., Goodman, S.N., Westra, W.H., Hoque, M.O. and Sidransky, D. (2011) An epigenetic marker panel for detection of lung cancer using cell-free serum DNA. Clin. Cancer Res. 17, 4494-4503
156. Breitling, L.P. (2013) Current genetics and epigenetics of smoking/tobacco-related cardiovascular disease. Arterioscler. Thromb. Vasc. Biol. 33, 1468-1472
157. Suter, M., Ma, J., Harris, A., Patterson, L., Brown, K.A., Shope, C., Showalter, L., Abramovici, A. and Aagaard-Tillery, K.M. (2011) Maternal tobacco use modestly alters correlated epigenome-wide placental DNA methylation and gene expression. Epigenetics 6, 1284-1294
158. Heil, M., Eitenmuller, I., Schmitz-Rixen, T. and Schaper, W. (2006) Arteriogenesis versus angiogenesis: similarities and differences. J. Cell. Mol. Med. 10, 45-55
159. Cai, W. and Schaper, W. (2008) Mechanisms of arteriogenesis. Acta Biochim. Biophys. Sin. 40, 681-692
160. Carmeliet, P. (2005) Angiogenesis in life, disease and medicine. Nature 438, 932-936
161. Katoh, M. (2013) Therapeutics targeting angiogenesis: genetics and epigenetics, extracellular miRNAs and signaling networks (review). Int. J. Mol. Med. 32, 763-767
162. Buysschaert, I., Schmidt, T., Roncal, C., Carmeliet, P. and Lambrechts, D. (2008) Genetics, epigenetics and pharmaco-(epi)genomics in angiogenesis. J. Cell. Mol. Med. 12, 2533-2551
163. Findeisen, H.M., Gizard, F., Zhao, Y., Qing, H., Heywood, E.B., Jones, K.L., Cohn, D. and Bruemmer, D. (2011) Epigenetic regulation of vascular smooth muscle cell proliferation and neointima formation by histone deacetylase inhibition. Arterioscler. Thromb. Vasc. Biol. 31, 851-860
164. Sambucetti, L.C., Fischer, D.D., Zabludoff, S., Kwon, P.O., Chamberlin, H., Trogani, N., Xu, H. and Cohen, D. (1999) Histone deacetylase inhibition selectively alters the activity and expression of cell cycle proteins leading to specific chromatin acetylation and antiproliferative effects. J. Biol. Chem. 274, 34940-34947
165. Mathew, O.P., Ranganna, K. and Yatsu, F.M. (2010) 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 64, 733-740
166. Owens, G.K., Kumar, M.S. and Wamhoff, B.R. (2004) Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol. Rev. 84, 767-801
167. Singh, N., Trivedi, C.M., Lu, M., Mullican, S.E., Lazar, M.A. and Epstein, J.A. (2011) Histone deacetylase 3 regulates smooth muscle differentiation in neural crest cells and development of the cardiac outflow tract. Circ. Res. 109, 1240-1249
168. Muzic, V., Katusic Bojanac, A., Juric-Lekic, G., Himelreich, M., Tupek, K., Serman, L., Marn, N., Sincic, N., Vlahovic, M. and Bulic-Jakus, F. (2013) Epigenetic drug 5-azacytidine impairs proliferation of rat limb buds in an organotypic model-system in vitro. Croat. Med. J. 54, 489-495
169. Shimamura, M., Nakagami, H., Sata, M., Takaoka, M., Azuma, J., Kiomy Osako, M., Koriyama, H., Kurinami, H., Wakayama, K., Miyake, T. and Morishita, R. (2013) Unique remodeling processes after vascular injury in intracranial arteries: analysis using a novel mouse model. J. Cereb. Blood Flow Metab. 33, 1153-1159
170. Shiva Shankar, T.V. and Willems, L. (2014) Epigenetic modulators mitigate angiogenesis through a complex transcriptomic network. Vascul. Pharmacol. 60, 57-66
171. Martinelli, S., Kanduri, M., Maffei, R., Fiorcari, S., Bulgarelli, J., Marasca, R. and Rosenquist, R. (2013) ANGPT2 promoter methylation is strongly associated with gene expression and prognosis in chronic lymphocytic leukemia. Epigenetics 8, 720-729
172. Liu, X., Zheng, N., Shi, Y.N., Yuan, J. and Li, L. (2014) Thyroid hormone induced angiogenesis through the integrin alphavbeta3/protein kinase D/histone deacetylase 5 signaling pathway. J. Mol. Endocrinol. 52, 245-254
173. Ungvari, Z., Tucsek, Z., Sosnowska, D., Toth, P., Gautam, T., Podlutsky, A., Csiszar, A., Losonczy, G., Valcarcel-Ares, M.N., Sonntag, W.E. and Csiszar, A. (2013) Aging-induced dysregulation of dicer1-dependent microRNA expression impairs angiogenic capacity of rat cerebromicrovascular endothelial cells. J. Gerontol. A Biol. Sci. Med. Sci. 68, 877-891
174. Mann, J., Chu, D.C., Maxwell, A., Oakley, F., Zhu, N.L., Tsukamoto, H. and Mann, D.A. (2010) MeCP2 controls an epigenetic pathway that promotes myofibroblast transdifferentiation and fibrosis. Gastroenterology 138, 705-714, 714 e1-4
175. Pang, M. and Zhuang, S. (2010) Histone deacetylase: a potential therapeutic target for fibrotic disorders. J. Pharmacol. Exp. Ther. 335, 266-272
176. Catania, A., Iavarone, C., Carlomagno, S.M. and Chiariello, M. (2006) Selective transcription and cellular proliferation induced by PDGF require histone deacetylase activity. Biochem. Biophys. Res. Commun. 343, 544-554
177. Ling, C. and Ronn, T. (2014) Epigenetic adaptation to regular exercise in humans. Drug Discov. Today 19, 1015-1018
178. Alibegovic, A.C., Hojbjerre, L., Sonne, M.P., van Hall, G., Stallknecht, B., Dela, F. and Vaag, A. (2009) Impact of 9 days of bed rest on hepatic and peripheral insulin action, insulin secretion, and whole-body lipolysis in healthy young male offspring of patients with type 2 diabetes. Diabetes 58, 2749-2756
179. Sanchis-Gomar, F., Garcia-Gimenez, J.L., Perez-Quilis, C., Gomez-Cabrera, M.C., Pallardo, F.V. and Lippi, G. (2012) Physical exercise as an epigenetic modulator: eustress, the "positive stress" as an effector of gene expression. J. Strength Condit. Res. 26, 3469-3472
180. Bloch, W., Suhr, F. and Zimmer, P. (2012) Molecular mechanisms of exercise-induced cardiovascular adaptations. Influence of epigenetics, mechanotransduction and free radicals. Herz 37, 508-515
181. Nakajima, K., Takeoka, M., Mori, M., Hashimoto, S., Sakurai, A., Nose, H., Higuchi, K., Itano, N., Shiohara, M., Oh, T. and Taniguchi, S. (2010) Exercise effects on methylation of ASC gene. Int. J. Sports Med. 31, 671-675
182. White, A.J., Sandler, D.P., Bolick, S.C., Xu, Z., Taylor, J.A. and DeRoo, L.A. (2013) Recreational and household physical activity at different time points and DNA global methylation. Eur. J. Cancer 49, 2199-2206
183. Zhang, F.F., Cardarelli, R., Carroll, J., Zhang, S., Fulda, K.G., Gonzalez, K., Vishwanatha, J.K., Morabia, A. and Santella, R.M. (2011) Physical activity and global genomic DNA methylation in a cancer-free population. Epigenetics. 6, 293-299
184. Nielsen, S., Scheele, C., Yfanti, C., Akerstrom, T., Nielsen, A.R., Pedersen, B.K. and Laye, M.J. (2010) Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle. J. Physiol. 588, 4029-4037
185. Barres, R., Yan, J., Egan, B., Treebak, J.T., Rasmussen, M., Fritz, T., Caidahl, K., Krook, A., O'Gorman, D.J. and Zierath, J.R. (2012) Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab. 15, 405-411
186. Ronn, T., Volkov, P., Davegardh, C., Dayeh, T., Hall, E., Olsson, A.H., Nilsson, E., Tornberg, A., Dekker Nitert, M., Eriksson, K.F. et al. (2013) A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet. 9, e1003572
187. Nitert, M.D., Dayeh, T., Volkov, P., Elgzyri, T., Hall, E., Nilsson, E., Yang, B.T., Lang, S., Parikh, H., Wessman, Y. et al. (2012) Impact of an exercise intervention on DNA methylation in skeletal muscle from first-degree relatives of patients with type 2 diabetes. Diabetes 61, 3322-3332
188. Gomez-Pinilla, F., Zhuang, Y., Feng, J., Ying, Z. and Fan, G. (2011) Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation. Eur. J. Neurosci. 33, 383-390
189. Abel, J.L. and Rissman, E.F. (2013) Running-induced epigenetic and gene expression changes in the adolescent brain. Int. J. Dev. Neurosci. 31, 382-390
190. Elsner, V.R., Lovatel, G.A., Moyses, F., Bertoldi, K., Spindler, C., Cechinel, L.R., Muotri, A.R. and Siqueira, I.R. (2013) Exercise induces age-dependent changes on epigenetic parameters in rat hippocampus: a preliminary study. Exp. Gerontol. 48, 136-139
191. Lovatel, G.A., Elsner, V.R., Bertoldi, K., Vanzella, C., Moyses Fdos, S., Vizuete, A., Spindler, C., Cechinel, L.R., Netto, C.A., Muotri, A.R. and Siqueira, I.R. (2013) Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus. Neurobiol. Learn. Mem. 101, 94-102
192. Heo, M. and Kim, E. (2013) Beneficial effects of antecedent exercise training on limb motor function and calpain expression in a rat model of stroke. J. Phys. Ther. Sci. 25, 943-946
193. Mascarenhas, J.V., Albayati, M.A., Shearman, C.P. and Jude, E.B. (2014) Peripheral arterial disease. Endocrinol. Metab. Clin. North Am. 43, 149-166
194. Gardner, A.W. and Poehlman, E.T. (1995) Exercise rehabilitation programs for the treatment of claudication pain. A meta-analysis. JAMA 274, 975-980
195. Radak, Z., Zhao, Z., Koltai, E., Ohno, H. and Atalay, M. (2013) Oxygen consumption and usage during physical exercise: the balance between oxidative stress and ROS-dependent adaptive signaling. Antioxid. Redox Signal. 18, 1208-1246
196. McGee, S.L., Fairlie, E., Garnham, A.P. and Hargreaves, M. (2009) Exercise-induced histone modifications in human skeletal muscle. J. Physiol. 587, 5951-5958
197. McKinsey, T.A., Zhang, C.L., Lu, J. and Olson, E.N. (2000) Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature 408, 106-111
198. Smith, J.A., Kohn, T.A., Chetty, A.K. and Ojuka, E.O. (2008) CaMK activation during exercise is required for histone hyperacetylation and MEF2A binding at the MEF2 site on the Glut4 gene. Am. J. Physiol. Endocrinol. Metab. 295, E698-E704
199. Potthoff, M.J., Wu, H., Arnold, M.A., Shelton, J.M., Backs, J., McAnally, J., Richardson, J.A., Bassel-Duby, R. and Olson, E.N. (2007) Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers. J. Clin. Invest. 117, 2459-2467
200. Rasmussen, M., Zierath, J.R. and Barres, R. (2014) Dynamic epigenetic responses to muscle contraction. Drug Discov. Today 19, 1010-1014
201. Tahiliani, M., Koh, K.P., Shen, Y., Pastor, W.A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L.M., Liu, D.R., Aravind, L. and Rao, A. (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324, 930-935
202. Davidsen, P.K., Gallagher, I.J., Hartman, J.W., Tarnopolsky, M.A., Dela, F., Helge, J.W., Timmons, J.A. and Phillips, S.M. (2011) High responders to resistance exercise training demonstrate differential regulation of skeletal muscle microRNA expression. J. Appl. Physiol. 110, 309-317
203. Pandey, D., Sikka, G., Bergman, Y., Kim, J.H., Ryoo, S., Romer, L. and Berkowitz, D. (2014) Transcriptional regulation of endothelial arginase 2 by histone deacetylase 2. Arterioscler. Thromb. Vasc. Biol. 34, 1556-1566
204. Jung, S.B., Kim, C.S., Naqvi, A., Yamamori, T., Mattagajasingh, I., Hoffman, T.A., Cole, M.P., Kumar, A., Dericco, J.S., Jeon, B.H. and Irani, K. (2010) Histone deacetylase 3 antagonizes aspirin-stimulated endothelial nitric oxide production by reversing aspirin-induced lysine acetylation of endothelial nitric oxide synthase. Circ. Res. 107, 877-887
205. Coppede, F. (2014) Epigenetic biomarkers of colorectal cancer: Focus on DNA methylation. Cancer Lett. 342, 238-247
206. Litzow, M.R. (2011) Novel therapeutic approaches for acute lymphoblastic leukemia. Hematol. Oncol. Clin. North Am. 25, 1303-1317
207. Kelly, W.K., Richon, V.M., O'Connor, O., Curley, T., MacGregor-Curtelli, B., Tong, W., Klang, M., Schwartz, L., Richardson, S., Rosa, E. et al. (2003) Phase I clinical trial of histone deacetylase inhibitor: suberoylanilide hydroxamic acid administered intravenously. Clin. Cancer Res. 9, 3578-3588
208. Kim, J., Kim, J.Y., Song, K.S., Lee, Y.H., Seo, J.S., Jelinek, J., Goldschmidt-Clermont, P.J. and Issa, J.P. (2007) Epigenetic changes in estrogen receptor beta gene in atherosclerotic cardiovascular tissues and in-vitro vascular senescence. Biochim. Biophys. Acta 1772, 72-80