Role of S-adenosylhomocysteine in cardiovascular disease and its potential epigenetic mechanism

International Journal of Biochemistry and Cell Biology

Volumn 67, Issue , 2015, Pages 158-166

  Xiao, Yunjun ^a   Su, Xuefen ^b   Huang, Wei ^a   Zhang, Jinzhou ^a   Peng, Chaoqiong ^a   Huang, Haixiong ^a   Wu, Xiaomin ^a   Huang, Haiyan ^a   Xia, Min ^c   Ling, Wenhua ^c  

^a SHENZHEN CENTER FOR DISEASE CONTROL AND PREVENTION   (China)

^b CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^c SUN YAT SEN UNIVERSITY   (China)

Author keywords

Atherosclerosis; Cardiovascular disease; Epigenetic; Homocysteine; S adenosylhomocysteine

Indexed keywords

BIOLOGICAL MARKER; HOMOCYSTEINE; METHIONINE; S ADENOSYLHOMOCYSTEINE; S ADENOSYLMETHIONINE;

ARTICLE; ATHEROSCLEROSIS; BLOOD LEVEL; CARDIOVASCULAR DISEASE; CELL LEVEL; DIABETES MELLITUS; ENDOTHELIAL DYSFUNCTION; EPIGENETICS; HUMAN; HYPERHOMOCYSTEINEMIA; KIDNEY DISEASE; METABOLISM; MOLECULAR BIOLOGY; NONHUMAN; OBESITY; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PROTEIN FUNCTION; REGULATORY MECHANISM; RISK FACTOR; GENETIC EPIGENESIS; GENETICS; PATHOLOGY; VASCULAR ENDOTHELIUM;

ATHEROSCLEROSIS; DIABETES MELLITUS; ENDOTHELIUM, VASCULAR; EPIGENESIS, GENETIC; HUMANS; HYPERHOMOCYSTEINEMIA; KIDNEY DISEASES; OBESITY; OXIDATIVE STRESS; S-ADENOSYLHOMOCYSTEINE; S-ADENOSYLMETHIONINE;

EID: 84940892633     PISSN: 13572725     EISSN: 18785875     Source Type: Journal    
DOI: 10.1016/j.biocel.2015.06.015     Document Type: Review

References (101)

1. C.M. Albert, N.R. Cook, J.M. Gaziano, E. Zaharris, J. MacFadyen, E. Danielson, and et al. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial JAMA 299 2008 2027 2036
2. A.I. Ara, M. Xia, K. Ramani, J.M. Mato, and S.C. Lu S-adenosylmethionine inhibits lipopolysaccharide-induced gene expression via modulation of histone methylation Hepatology 47 2008 1655 1666
3. H. Ariyama, N. Kono, S. Matsuda, T. Inoue, and H. Arai Decrease in membrane phospholipid unsaturation induces unfolded protein response J. Biol. Chem. 285 2010 22027 22035
4. R.C. Austin, S.R. Lentz, and G.H. Werstuck Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease Cell Death Differ. 11 Suppl. 1 2004 S56 S64
5. M. Barroso, C. Florindo, H. Kalwa, Z. Silva, A.A. Turanov, B.A. Carlson, and et al. Inhibition of cellular methyltransferases promotes endothelial cell activation by suppressing glutathione peroxidase 1 protein expression J. Biol. Chem. 289 2014 15350 15362
6. A. Becker, R.M. Henry, P.J. Kostense, C. Jakobs, T. Teerlink, S. Zweegman, and et al. Plasma homocysteine and S-adenosylmethionine in erythrocytes as determinants of carotid intima-media thickness: different effects in diabetic and non-diabetic individuals. The Hoorn Study Atherosclerosis 169 2003 323 330
7. A. Becker, Y.M. Smulders, T. Teerlink, E.A. Struys, K. de Meer, P.J. Kostense, and et al. S-adenosylhomocysteine and the ratio of S-adenosylmethionine to S-adenosylhomocysteine are not related to folate, cobalamin and vitamin B6 concentrations Eur. J. Clin. Invest. 33 2003 17 25
8. B.E. Bernstein, A. Meissner, and E.S. Lander The mammalian epigenome Cell 128 2007 669 681
9. S.R. Bhaumik, E. Smith, and A. Shilatifard Covalent modifications of histones during development and disease pathogenesis Nat. Struct. Mol. Biol. 14 2007 1008 1016
10. A. Bird DNA methylation patterns and epigenetic memory Genes Dev. 16 2002 6 21
11. R.H. Boger, S.M. Bode-Boger, K. Sydow, D.D. Heistad, and S.R. Lentz Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in monkeys with hyperhomocyst(e)inemia or hypercholesterolemia Arterioscler. Thromb. Vasc. Biol. 20 2000 1557 1564
12. K.H. Bonaa, I. Njolstad, P.M. Ueland, H. Schirmer, A. Tverdal, T. Steigen, and et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction N. Engl. J. Med. 354 2006 1578 1588
13. L. Brattstrom, and D.E. Wilcken Homocysteine and cardiovascular disease: cause or effect? Am. J. Clin. Nutr. 72 2000 315 323
14. R. Castro, I. Rivera, C. Martins, E.A. Struys, E.E. Jansen, N. Clode, and et al. Intracellular S-adenosylhomocysteine increased levels are associated with DNA hypomethylation in HUVEC J. Mol. Med. 83 2005 831 836
15. R. Castro, I. Rivera, E.A. Struys, E.E. Jansen, P. Ravasco, M.E. Camilo, and et al. Increased homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease Clin. Chem. 49 2003 1292 1296
16. M.A. Caudill, J.C. Wang, S. Melnyk, I.P. Pogribny, S. Jernigan, M.D. Collins, and et al. Intracellular S-adenosylhomocysteine concentrations predict global DNA hypomethylation in tissues of methyl-deficient cystathionine beta-synthase heterozygous mice J. Nutr. 131 2001 2811 2818
17. G.C. Chan, J.E. Fish, I.A. Mawji, D.D. Leung, A.C. Rachlis, and P.A. Marsden Epigenetic basis for the transcriptional hyporesponsiveness of the human inducible nitric oxide synthase gene in vascular endothelial cells J. Immunol. 175 2005 3846 3861
18. Z. Chen, A.C. Karaplis, S.L. Ackerman, I.P. Pogribny, S. Melnyk, S. Lussier-Cacan, and et al. Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition Hum. Mol. Genet. 10 2001 433 443
19. S.F. Choumenkovitch, J. Selhub, P.J. Bagley, N. Maeda, M.R. Nadeau, D.E. Smith, and et al. In the cystathionine beta-synthase knockout mouse, elevations in total plasma homocysteine increase tissue S-adenosylhomocysteine, but responses of S-adenosylmethionine and DNA methylation are tissue specific J. Nutr. 132 2002 2157 2160
20. R. Clarke, L. Daly, K. Robinson, E. Naughten, S. Cahalane, B. Fowler, and et al. Hyperhomocysteinemia: an independent risk factor for vascular disease N. Engl. J. Med. 324 1991 1149 1155
21. R. Clarke, J. Halsey, S. Lewington, E. Lonn, J. Armitage, J.E. Manson, and et al. Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: meta-analysis of 8 randomized trials involving 37 485 individuals Arch. Intern. Med. 170 2010 1622 1631
22. S. Dayal, T. Bottiglieri, E. Arning, N. Maeda, M.R. Malinow, C.D. Sigmund, and et al. Endothelial dysfunction and elevation of S-adenosylhomocysteine in cystathionine beta-synthase-deficient mice Circ. Res. 88 2001 1203 1209
23. A.S. De Vriese, H.J. Blom, S.G. Heil, S. Mortier, L.A. Kluijtmans, J. Van de Voorde, and et al. Endothelium-derived hyperpolarizing factor-mediated renal vasodilatory response is impaired during acute and chronic hyperhomocysteinemia Circulation 109 2004 2331 2336
24. S. Doshi, I. McDowell, J. Goodfellow, S. Stabler, R. Boger, R. Allen, and et al. Relationship between S-adenosylmethionine, S-adenosylhomocysteine, asymmetric dimethylarginine, and endothelial function in healthy human subjects during experimental hyper- and hypohomocysteinemia Metab. Clin. Exp. 54 2005 351 360
25. R.T. Eberhardt, M.A. Forgione, A. Cap, J.A. Leopold, M.A. Rudd, M. Trolliet, and et al. Endothelial dysfunction in a murine model of mild hyperhomocyst(e)inemia J. Clin. Invest. 106 2000 483 491
26. A.K. Elshorbagy, C. Church, M. Valdivia-Garcia, A.D. Smith, H. Refsum, and R. Cox Dietary cystine level affects metabolic rate and glycaemic control in adult mice J. Nutr. Biochem. 23 2012 332 340
27. A.K. Elshorbagy, G. Nijpels, M. Valdivia-Garcia, C.D. Stehouwer, M. Ocke, H. Refsum, and et al. S-adenosylmethionine is associated with fat mass and truncal adiposity in older adults J. Nutr. 143 2013 1982 1988
28. A.K. Elshorbagy, E. Nurk, C.G. Gjesdal, G.S. Tell, P.M. Ueland, O. Nygard, and et al. Homocysteine, cysteine, and body composition in the Hordaland Homocysteine Study: does cysteine link amino acid and lipid metabolism? Am. J. Clin. Nutr. 88 2008 738 746
29. A.K. Elshorbagy, M. Valdivia-Garcia, I.M. Graham, R. Palma Reis, A. Sales Luis, A.D. Smith, and et al. The association of fasting plasma sulfur-containing compounds with BMI, serum lipids and apolipoproteins Nutr. Metab. Cardiovasc. Dis. 22 2012 1031 1038
30. F. Esfandiari, V. Medici, D.H. Wong, S. Jose, M. Dolatshahi, E. Quinlivan, and et al. Epigenetic regulation of hepatic endoplasmic reticulum stress pathways in the ethanol-fed cystathionine beta synthase-deficient mouse Hepatology 51 2010 932 941
31. M. Fatemi, A. Hermann, H. Gowher, and A. Jeltsch Dnmt3a and Dnmt1 functionally cooperate during de novo methylation of DNA Eur. J. Biochem. 269 2002 4981 4984
32. R.H. Fryer, B.D. Wilson, D.B. Gubler, L.A. Fitzgerald, and G.M. Rodgers Homocysteine, a risk factor for premature vascular disease and thrombosis, induces tissue factor activity in endothelial cells Arterioscler. Thromb. 13 1993 1327 1333
33. G. Garibotto, A. Valli, B. Anderstam, M. Eriksson, M.E. Suliman, M. Balbi, and et al. The kidney is the major site of S-adenosylhomocysteine disposal in humans Kidney Int. 76 2009 293 296
34. H. Gellekink, D. van Oppenraaij-Emmerzaal, A. van Rooij, E.A. Struys, M. den Heijer, and H.J. Blom Stable-isotope dilution liquid chromatography-electrospray injection tandem mass spectrometry method for fast, selective measurement of S-adenosylmethionine and S-adenosylhomocysteine in plasma Clin. Chem. 51 2005 1487 1492
35. T.J. Green, C.M. Skeaff, J.A. McMahon, B.J. Venn, S.M. Williams, A.M. Devlin, and et al. Homocysteine-lowering vitamins do not lower plasma S-adenosylhomocysteine in older people with elevated homocysteine concentrations Br. J. Nutr. 103 2010 1629 1634
36. M.A. Grillo, and S. Colombatto S-adenosylmethionine and its products Amino Acids 34 2008 187 193
37. M.G. Guenther, S.S. Levine, L.A. Boyer, R. Jaenisch, and R.A. Young A chromatin landmark and transcription initiation at most promoters in human cells Cell 130 2007 77 88
38. K. Hensley, J.M. Carney, M.P. Mattson, M. Aksenova, M. Harris, J.F. Wu, and et al. A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease Proc. Natl. Acad. Sci. U. S. A. 91 1994 3270 3274
39. M. Hermes, H. Geisler, H. Osswald, R. Riehle, and D. Kloor Alterations in S-adenosylhomocysteine metabolism decrease O6-methylguanine DNA methyltransferase gene expression without affecting promoter methylation Biochem. Pharmacol. 75 2008 2100 2111
40. W. Herrmann, H. Schorr, R. Obeid, J. Makowski, B. Fowler, and M.K. Kuhlmann Disturbed homocysteine and methionine cycle intermediates S-adenosylhomocysteine and S-adenosylmethionine are related to degree of renal insufficiency in type 2 diabetes Clin. Chem. 51 2005 891 897
41. G.S. Hotamisligil Endoplasmic reticulum stress and the inflammatory basis of metabolic disease Cell 140 2010 900 917
42. G.S. Hotamisligil Endoplasmic reticulum stress and atherosclerosis Nat. Med. 16 2010 396 399
43. S.M. Innis, A.G. Davidson, A. Chen, R. Dyer, S. Melnyk, and S.J. James Increased plasma homocysteine and S-adenosylhomocysteine and decreased methionine is associated with altered phosphatidylcholine and phosphatidylethanolamine in cystic fibrosis J. Pediatr. 143 2003 351 356
44. M. Inoue-Choi, H.H. Nelson, K. Robien, E. Arning, T. Bottiglieri, W.P. Koh, and et al. One-carbon metabolism nutrient status and plasma S-adenosylmethionine concentrations in middle-aged and older Chinese in Singapore Int. J. Mol. Epidemiol. Genet. 3 2012 160 173
45. K. Jabs, M.J. Koury, W.D. Dupont, and C. Wagner Relationship between plasma S-adenosylhomocysteine concentration and glomerular filtration rate in children Metab. Clin. Exp. 55 2006 252 257
46. S.J. James, S. Melnyk, M. Pogribna, I.P. Pogribny, and M.A. Caudill Elevation in S-adenosylhomocysteine and DNA hypomethylation: potential epigenetic mechanism for homocysteine-related pathology J. Nutr. 132 2002 2361S 2366S
47. R.L. Jamison, P. Hartigan, J.S. Kaufman, D.S. Goldfarb, S.R. Warren, P.D. Guarino, and et al. Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial JAMA 298 2007 1163 1170
48. Y. Jiang, T. Sun, J. Xiong, J. Cao, G. Li, and S. Wang Hyperhomocysteinemia-mediated DNA hypomethylation and its potential epigenetic role in rats Acta Biochim. Biophys. Sin. 39 2007 657 667
49. P.M. Kanani, C.A. Sinkey, R.L. Browning, M. Allaman, H.R. Knapp, and W.G. Haynes Role of oxidant stress in endothelial dysfunction produced by experimental hyperhomocyst(e)inemia in humans Circulation 100 1999 1161 1168
50. S.S. Kang, P.W.K. Wong, and M.R. Malinow Hyperhomocyst(e)inemia as a risk factor for occlusive vascular disease Annu. Rev. Nutr. 12 1992 279 298
51. B.P. Kennedy, T. Bottiglieri, E. Arning, M.G. Ziegler, L.A. Hansen, and E. Masliah Elevated S-adenosylhomocysteine in Alzheimer brain: influence on methyltransferases and cognitive function J. Neural Transm. 111 2004 547 567
52. D.M. Kerins, M.J. Koury, A. Capdevila, S. Rana, and C. Wagner Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine Am. J. Clin. Nutr. 74 2001 723 729
53. J.K. Lee, and K.C. Kim DZNep, inhibitor of S-adenosylhomocysteine hydrolase, down-regulates expression of SETDB1 H3K9me3 HMTase in human lung cancer cells Biochem. Biophys. Res. Commun. 438 2013 647 652
54. H.C. Lin, T.Y. Song, and M.L. Hu S-Adenosylhomocysteine enhances DNA damage through increased beta-amyloid formation and inhibition of the DNA-repair enzyme OGG1b in microglial BV-2 cells Toxicology 290 2011 342 349
55. P.Y. Lin, T.H. Yang, H.G. Lin, and M.L. Hu Synergistic effects of S-adenosylhomocysteine and homocysteine on DNA damage in a murine microglial cell line Clin. Chim. Acta 379 2007 139 144
56. C. Liu, Q. Wang, H. Guo, M. Xia, Q. Yuan, Y. Hu, and et al. Plasma S-adenosylhomocysteine is a better biomarker of atherosclerosis than homocysteine in apolipoprotein E-deficient mice fed high dietary methionine J. Nutr. 138 2008 311 315
57. F.M. Loehrer, C.P. Angst, F.P. Brunner, W.E. Haefeli, and B. Fowler Evidence for disturbed S-adenosylmethionine: S-adenosylhomocysteine ratio in patients with end-stage renal failure: a cause for disturbed methylation reactions? Nephrol. Dial. Transplant. 13 1998 656 661
58. F.M. Loehrer, M. Tschopl, C.P. Angst, P. Litynski, K. Jager, B. Fowler, and et al. Disturbed ratio of erythrocyte and plasma S-adenosylmethionine/S-adenosylhomocysteine in peripheral arterial occlusive disease Atherosclerosis 154 2001 147 154
59. E. Lonn, S. Yusuf, M.J. Arnold, P. Sheridan, J. Pogue, M. Micks, and et al. Homocysteine lowering with folic acid and B vitamins in vascular disease N. Engl. J. Med. 354 2006 1567 1577
60. J. Loscalzo Homocysteine trials - clear outcomes for complex reasons N. Engl. J. Med. 354 2006 1629 1632
61. S.C. Lu, Y.J. Chen, and P.Y. Chang Letter to the editor: is homocysteine the culprit molecule in vascular diseases or just a bystander? Am. J. Physiol. Cell Physiol. 299 2010 C873 author reply C4
62. X. Luo, Y. Xiao, F. Song, Y. Yang, M. Xia, and W. Ling Increased plasma S-adenosyl-homocysteine levels induce the proliferation and migration of VSMCs through an oxidative stress-ERK1/2 pathway in apoE(-/-) mice Cardiovasc. Res. 95 2012 241 250
63. A.J. Lusis Atherosclerosis Nature 407 2000 233 241
64. M.A. Mansoor, C. Bergmark, A.M. Svardal, P.E. Lonning, and P.M. Ueland Redox status and protein binding of plasma homocysteine and other aminothiols in patients with early-onset peripheral vascular disease. Homocysteine and peripheral vascular disease Arterioscler. Thromb. Vasc. Biol. 15 1995 232 240
65. C.C. Matouk, and P.A. Marsden Epigenetic regulation of vascular endothelial gene expression Circ. Res. 102 2008 873 887
66. K.S. McCully Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis Am. J. Pathol. 56 1969 111 128
67. S. Ngo, X. Li, R. O'Neill, C. Bhoothpur, P. Gluckman, and A. Sheppard Elevated S-adenosylhomocysteine alters adipocyte functionality with corresponding changes in gene expression and associated epigenetic marks Diabetes 63 2014 2273 2283
68. M.A. Reddy, L.M. Villeneuve, M. Wang, L. Lanting, and R. Natarajan Role of the lysine-specific demethylase 1 in the proinflammatory phenotype of vascular smooth muscle cells of diabetic mice Circ. Res. 103 2008 615 623
69. V. Schachinger, M.B. Britten, and A.M. Zeiher Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease Circulation 101 2000 1899 1906
70. M.L. Selley Increased concentrations of homocysteine and asymmetric dimethylarginine and decreased concentrations of nitric oxide in the plasma of patients with Alzheimer's disease Neurobiol. Aging 24 2003 903 907
71. M.L. Selley A metabolic link between S-adenosylhomocysteine and polyunsaturated fatty acid metabolism in Alzheimer's disease Neurobiol. Aging 28 2007 1834 1839
72. J.A. Sipkens, N.E. Hahn, H.J. Blom, S.M. Lougheed, C.D. Stehouwer, J.A. Rauwerda, and et al. S-Adenosylhomocysteine induces apoptosis and phosphatidylserine exposure in endothelial cells independent of homocysteine Atherosclerosis 221 2012 48 54
73. A.M. Spijkerman, Y.M. Smulders, P.J. Kostense, R.M. Henry, A. Becker, T. Teerlink, and et al. S-adenosylmethionine and 5-methyltetrahydrofolate are associated with endothelial function after controlling for confounding by homocysteine: the Hoorn Study Arterioscler. Thromb. Vasc. Biol. 25 2005 778 784
74. F. Stam, C. van Guldener, P.M. ter Wee, W. Kulik, D.E. Smith, C. Jakobs, and et al. Homocysteine clearance and methylation flux rates in health and end-stage renal disease: association with S-adenosylhomocysteine Am. J. Physiol. Renal Physiol. 287 2004 F215 F223
75. G. Starkebaum, and J.M. Harlan Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine J. Clin. Invest. 77 1986 1370 1376
76. M.M. Steed, and S.C. Tyagi Mechanisms of cardiovascular remodeling in hyperhomocysteinemia Antioxid. Redox Signal. 15 2011 1927 1943
77. M.H. Stipanuk Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine Annu. Rev. Nutr. 24 2004 539 577
78. E.A. Struys, E.E. Jansen, K. de Meer, and C. Jakobs Determination of S-adenosylmethionine and S-adenosylhomocysteine in plasma and cerebrospinal fluid by stable-isotope dilution tandem mass spectrometry Clin. Chem. 46 2000 1650 1656
79. D.A. Swanson, M.L. Liu, P.J. Baker, L. Garrett, M. Stitzel, J. Wu, and et al. Targeted disruption of the methionine synthase gene in mice Mol. Cell. Biol. 21 2001 1058 1065
80. J. Tao, M. Yang, Z. Chen, Y. Huang, Q. Zhao, J. Xu, and et al. Decreased DNA methyltransferase 3A and 3B mRNA expression in peripheral blood mononuclear cells and increased plasma SAH concentration in adult patients with idiopathic thrombocytopenic purpura J. Clin. Immunol. 28 2008 432 439
81. A.M. Troen, E. Lutgens, D.E. Smith, I.H. Rosenberg, and J. Selhub The atherogenic effect of excess methionine intake Proc. Natl. Acad. Sci. U. S. A. 100 2003 15089 15094
82. N. Tyagi, A.V. Ovechkin, D. Lominadze, K.S. Moshal, and S.C. Tyagi Mitochondrial mechanism of microvascular endothelial cells apoptosis in hyperhomocysteinemia J. Cell. Biochem. 98 2006 1150 1162
83. P.M. Ueland, H. Refsum, S.A. Beresford, and S.E. Vollset The controversy over homocysteine and cardiovascular risk Am. J. Clin. Nutr. 72 2000 324 332
84. A. Valli, J.J. Carrero, A.R. Qureshi, G. Garibotto, P. Barany, J. Axelsson, and et al. Elevated serum levels of S-adenosylhomocysteine, but not homocysteine, are associated with cardiovascular disease in stage 5 chronic kidney disease patients Clin. Chim. Acta 395 2008 106 110
85. L.M. van Driel, M.J. Eijkemans, R. de Jonge, J.H. de Vries, J.B. van Meurs, E.A. Steegers, and et al. Body mass index is an important determinant of methylation biomarkers in women of reproductive ages J. Nutr. 139 2009 2315 2321
86. L.M. Villeneuve, M.A. Reddy, L.L. Lanting, M. Wang, L. Meng, and R. Natarajan 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 2008 9047 9052
87. C. Wagner, and M.J. Koury S-Adenosylhomocysteine: a better indicator of vascular disease than homocysteine? Am. J. Clin. Nutr. 86 2007 1581 1585
88. C. Wagner, W.J. Stone, M.J. Koury, W.D. Dupont, and D.M. Kerins S-adenosylhomocysteine is a more sensitive indicator of renal insufficiency than homocysteine Nutr. Res. 24 2004 487 494
89. D.S. Wald, A. Kasturiratne, and M. Simmonds Serum homocysteine and dementia: meta-analysis of eight cohort studies including 8669 participants Alzheimers Dement. 7 2011 412 417
90. H. Wang, X. Jiang, F. Yang, J.W. Gaubatz, L. Ma, M.J. Magera, and et al. Hyperhomocysteinemia accelerates atherosclerosis in cystathionine beta-synthase and apolipoprotein E double knock-out mice with and without dietary perturbation Blood 101 2003 3901 3907
91. M. Watanabe, J. Osada, Y. Aratani, K. Kluckman, R. Reddick, M.R. Malinow, and et al. Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia Proc. Natl. Acad. Sci. U. S. A. 92 1995 1585 1589
92. N. Weiss, S. Heydrick, Y.Y. Zhang, C. Bierl, A. Cap, and J. Loscalzo Cellular redox state and endothelial dysfunction in mildly hyperhomocysteinemic cystathionine beta-synthase-deficient mice Arterioscler. Thromb. Vasc. Biol. 22 2002 34 41
93. E.P. Wijekoon, M.E. Brosnan, and J.T. Brosnan Homocysteine metabolism in diabetes Biochem. Soc. Trans. 35 2007 1175 1179
94. K.M. Wilson, R.B. McCaw, L. Leo, E. Arning, S. Lhotak, T. Bottiglieri, and et al. Prothrombotic effects of hyperhomocysteinemia and hypercholesterolemia in ApoE-deficient mice Arterioscler. Thromb. Vasc. Biol. 27 2007 233 240
95. Y. Xiao, W. Huang, J. Zhang, C. Peng, M. Xia, and W. Ling Increased plasma S-adenosylhomocysteine-accelerated atherosclerosis is associated with epigenetic regulation of endoplasmic reticulum stress in apoE-/- mice Arterioscler. Thromb. Vasc. Biol. 35 2015 60 70
96. Y. Xiao, Y. Zhang, M. Wang, X. Li, D. Su, J. Qiu, and et al. Plasma S-adenosylhomocysteine is associated with the risk of cardiovascular events in patients undergoing coronary angiography: a cohort study Am. J. Clin. Nutr. 98 2013 1162 1169
97. T.H. Yang, N.C. Yang, and M.L. Hu S-adenosylhomocysteine enhances hydrogen peroxide-induced DNA damage by inhibition of DNA repair in two cell lines Nutr. Cancer 47 2003 70 75
98. P. Yi, S. Melnyk, M. Pogribna, I.P. Pogribny, R.J. Hine, and S.J. James Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation J. Biol. Chem. 275 2000 29318 29323
99. A.M. Zawada, K.S. Rogacev, B. Hummel, J.T. Berg, A. Friedrich, H.J. Roth, and et al. S-adenosylhomocysteine is associated with subclinical atherosclerosis and renal function in a cardiovascular low-risk population Atherosclerosis 234 2014 17 22
100. J. Zhou, J. Moller, C.C. Danielsen, J. Bentzon, H.B. Ravn, R.C. Austin, and et al. Dietary supplementation with methionine and homocysteine promotes early atherosclerosis but not plaque rupture in ApoE-deficient mice Arterioscler. Thromb. Vasc. Biol. 21 2001 1470 1476
101. J. Zhou, G.H. Werstuck, S. Lhotak, A.B. de Koning, S.K. Sood, G.S. Hossain, and et al. Association of multiple cellular stress pathways with accelerated atherosclerosis in hyperhomocysteinemic apolipoprotein E-deficient mice Circulation 110 2004 207 213