Cardiovascular pathogenesis in hyperhomocysteinemia

Increased plasma homocysteine (Hcy) is a significant and independent risk factor for cardiovascular disease. It can cause multi-disease manifestations such as smooth muscle proliferation, premature occlusive vascular disease, progressive arterial stenosis, haemostatic changes, placental vasculopathy, spontaneous early abortion, birth defects, impaired cognitive function and dementia. This review paper summarizes the role of elevated Hcy levels in cardiovascular and other diseases and the molecular mechanisms and pathophysiology involved in the deleterious manifestations of hyperhomocysteinemia. We have collected data from MEDLINE, Current Contents and scientific journals, which included 112 publications from 1932 to 2007. Cardiovascular pathophysiology in hyperhomocysteinemia is a complicated process, possibly due to direct toxicity of Hcy on tissues, low S-adenosylmethionine, high S-adenosylhomocysteine or thrombotic events triggered by stimulation of procoagulant factors and suppression of anticoagulant factors and platelet activation, thereby enhancing oxidative stress, smooth muscle cell proliferation, formation of reactive oxygen species, hypomethylation, induction of unfolded protein responses and extracellular matrix modification. The mechanisms involved in the increased risk of cardiovascular disease still remains a mystery in many respects, and more studies are needed to elucidate this association.