کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5947267 1172367 2013 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The potential role of homocysteine mediated DNA methylation and associated epigenetic changes in abdominal aortic aneurysm formation
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
The potential role of homocysteine mediated DNA methylation and associated epigenetic changes in abdominal aortic aneurysm formation
چکیده انگلیسی

Previous studies have suggested that homocysteine (Hcy) has wide-ranging biological effects, including accelerating atherosclerosis, impairing post injury endothelial repair and function, deregulating lipid metabolism and inducing thrombosis. However, the biochemical basis by which hyperhomocysteinemia (HHcy) contributes to cardiovascular diseases (CVDs) remains largely unknown. Several case-control studies have reported an association between HHcy and the presence of abdominal aortic aneurysms (AAA) and there are supportive data from animal models. Genotypic data concerning the association between variants of genes involved in the methionine cycle and AAA are conflicting probably due to problems such as reverse causality and confounding. The multifactorial nature of AAA suggests the involvement of additional epigenetic factors in disease formation. Elevated Hcy levels have been previously linked to altered DNA methylation levels in various diseases. Folate or vitamin B12 based methods of lowering Hcy have had disappointingly limited effects in reducing CVD events. One possible reason for the limited efficacy of such therapy is that they have failed to reverse epigenetic changes induced by HHcy. It is possible that individuals with HHcy have an “Hcy memory effect” due to epigenetic alterations which continue to promote progression of cardiovascular complications even after Hcy levels are lowered. It is possible that deleterious effect of prior, extended exposure to elevated Hcy concentrations have long-lasting effects on target organs and genes, hence underestimating the benefit of Hcy lowering therapies in CVD patients. Therapies targeting the epigenetic machinery as well as lowering circulating Hcy concentrations may have a more efficacious effect in reducing the incidence of cardiovascular complications.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Atherosclerosis - Volume 228, Issue 2, June 2013, Pages 295-305
نویسندگان
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