Notable epigenetic role of hyperhomocysteinemia in atherogenesis

Abstract

Atherosclerosis is associated with multiple genetic and modifiable risk factors. There is an increasing body of evidences to indicate that epigenetic mechanisms also play an essential role in atherogenesis by influencing gene expression. Homocysteine is a sulfur-containing amino acid formed during methionine metabolism. Elevated plasma level of homocysteine is generally termed as hyperhomocysteinemia. As a potential risk factor for cardiovascular diseases, hyperhomocysteinemia may initiate or motivate atherogenesis by modification of DNA methylation. The underlying epigenetic mechanism is still unclear with controversial findings. This review focuses on epigenetic involvement and mechanisms of hyperhomocysteinemia in atherogenesis. Considering the potential beneficial effects of anti-homocysteinemia treatments in preventing atherosclerosis, further studies on the role of hyperhomocysteinemia in atherogenesis are warranted.

Blood homocysteine, folic acid, vitamin B12 and vitamin B6 levels in psoriasis patients

“…The prevalence of hyperhomocysteinemia in the general population is 5% 35 . One of the congenital causes of high homocysteine is homocystinuria that occurs as a result of cystathionine β synthase defect and its incidence is 1:200.000.…”

“…Studies are being carried out in recent years to reveal whether or not high homocysteine contributes to atherogenesis through DNA hypomethylation 35 .…”

“…Besides CVD, other conditions causing or accompanying hyperhomocysteinemia include folate, vitamin B6 and vitamin B12 deficiencies associated with poor dietary intake as well as, smoking, alcohol and coffee consumption, advanced age, menopause, renal failure, autoimmune diseases, diabetes mellitus, osteoporosis, neuropsychiatric disorders, cancer, thyroid diseases, birth defects, and various medications 6,11,35 . Conditions causing elevated homocysteine include genetic defects of enzymes such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase and cystathionine β synthase 11 .…”

Fetal Origins of Obesity, Cardiovascular Disease, and Type 2 Diabetes

“…Homocysteine and vitamin B 6 are two examples that are described in human cross-sectional studies assessing immediate effects on health at one time point within a single generation. Hyperhomocysteinemia has been associated with hypomethylation in several studies [52] supporting the hypothesis that epigenetic mechanisms may play a partial role in observed associations between hyperhomocysteinemia and decreased cardiovascular health via inflammation, free radical formation, and atherogenesis [53]. Low vitamin B 6 levels may decrease N 5,10 -methenyl-THF through reduced serine hydroxymethyltransferase (SHMT) activity (Figure 22.4), stressing the thymidylate synthase pathway for DNA repair and incorporating more uracil into DNA.…”

Homocysteine — is it still an important risk factor for cardiovascular disease?

“…A number of mechanisms have been suggested including intracellular production of free oxygen species, inhibition of nitric oxide synthesis, activation of thrombosis, endothelial dysfunction, monocyte activation, production of inflammatory mediators including interleukin-8 and haeme carrier protein (HCP-1), and stimulation of smooth muscle cell proliferation [32,33]. Complex links between hyperhomocysteinaemia and atherosclerosis may also be mediated by endothelial cell DNA hypomethylation associated with accumulation of SAH [34,35]. SAH is a strong inhibitor of intracellular methylotransferases including DNA methylotransferase.…”