Homocysteine and vascular dysfunction.
Elevated plasma levels of homocysteine and disulfide adducts of homocysteine (collectively termed "homocyst(e)ine") are associated with increased risk of thrombotic and atherosclerotic vascular disease. It is still not evident, however, whether moderately elevated plasma homocyst(e)ine concentration per se is a cause, or rather just a marker for an associated condition that may predispose to development of vascular disease or its complications. This distinction has important clinical consequences, since dietary intervention to lower plasma homocyst(e)ine has been proposed as a global strategy to decrease the prevalence of vascular disease. Studies of cultured cells in vitro have led to the hypothesis that homocysteine may predispose to vascular disease by altering the normally antithrombotic and vasoprotective phenotype of vascular endothelium, perhaps through a mechanism that involves generation of peroxides and other reactive oxygen species. Recent findings in animal and human models of moderate hyperhomocyst(e)inemia provide support for some aspects of this hypothesis. Endothelial dysfunction in hyperhomocyst(e)inemia may contribute to development of atherosclerosis and predispose to complications such as thrombosis and vasospasm. Important questions to be addressed in future investigations include the relative importance of homocysteine versus associated conditions (such as folate deficiency) in the etiology of vascular dysfunction, the role of homocysteine-induced oxidant stress, and the potential benefits of lowering plasma homocyst(e)ine levels through dietary supplementation with B vitamins.
Lentz
S R
SR
Veterans Affairs Medical Center, Iowa City, IA 52246, USA. steven-lentz@uiowa.edu
D000818:Animals; D001161:Arteriosclerosis; D004220:Disulfides / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology; D006710:Homocysteine / Q000097:blood* / Q000502:physiology; D006801:Humans; D013927:Thrombosis; D014652:Vascular Diseases / Q000097:blood* / Q000503:physiopathology
D004220:Disulfides; D006710:Homocysteine