title: Abnormalities of vascular function in hyperhomocysteinaemia: relationship to atherothrombotic disease.
abstract: Hyperhomocysteinaemia is a risk factor for atherothrombotic disease, but data are limited on the arterial histology in humans with hyperhomocysteinaemia, either with or without other risk factors. Studies in vitro and in animals have shown that hyperhomocysteinaemia, possibly by increasing oxidant stress as well as by other mechanisms, may induce dysfunction of the vascular endothelium and proliferation of vascular smooth muscle cells, both key processes in atherogenesis. In clinically healthy subjects with hyperhomocysteinaemia, endothelium-dependent vasodilation may be impaired, but endothelial antithrombotic and profibrinolytic function appear normal at this stage. In patients with atherosclerosis and hyperhomocysteinaemia, endothelial antithrombotic properties appear more severely impaired than in similar patients with normohomocysteinaemia. Controlled data on the effects of homocysteine-lowering treatment on vascular function in humans are not available. The increased risk of atherothrombotic disease conferred by hyperhomocysteinaemia may be related to homocysteine-associated impairments in endothelial and vascular smooth muscle cell function. The precise mechanisms by which homocysteine affects vascular cell function, however, are unknown.
authors.affiliation: Department of Internal Medicine, Academisch Ziekenhuis Vrije Universiteit, and Institute for Cardiovascular Research, Amsterdam, The Netherlands.
authors.forename: C D
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000097:blood* / Q000503:physiopathology; D001682:Biological Availability; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology; D005342:Fibrinolysis; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D017942:Nitric Acid / Q000378:metabolism; D015539:Platelet Activation; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood* / Q000503:physiopathology; D014664:Vasodilation
chemical_list: D006710:Homocysteine; D017942:Nitric Acid