Hyperhomocysteinemia and atherothrombotic disease.
Hyperhomocysteinemia is an independent risk factor for atherothrombotic disease. The mechanism by which homocysteine induces atherosclerosis and thrombosis is not fully understood. Data on arterial histology in humans with homocystinuria and mild hyperhomocysteinemia are limited. In vitro studies as well as studies in animals and humans indicate that hyperhomocysteinemia induces dysfunction of the vascular endothelium, with loss of endothelium-dependent vasodilation and endothelial antithrombotic properties, and proliferation of vascular smooth muscle cells, which are key processes in current models of atherogenesis and thrombosis. One of the hypotheses is that homocysteine can lead to cellular dysfunction through a mechanism involving oxidative damage but future studies in humans are needed to confirm this. Studies in hyperhomocysteinemic vascular patients have shown that endothelial antithrombotic properties appear to be more severely impaired than in similar patients with normohomocysteinemia. Furthermore, impaired endothelium-dependent vasodilation has been observed in clinically healthy hyperhomocysteinemic subjects in whom no abnormalities were found in endothelial antithrombotic properties. Future studies involving homocysteine-lowering treatment in hyperhomocysteinemic patients with vascular disease and in clinically healthy hyperhomocysteinemic subjects are necessary to investigate the mechanisms by which homocysteine causes atherothrombotic disorders in humans.
Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands.
S C
SC
de Jong
M
M
van den Berg
J A
JA
Rauwerda
C D
CD
Stehouwer
D001161:Arteriosclerosis / Q000209:etiology* / Q000503:physiopathology; D001779:Blood Coagulation Factors / Q000502:physiology; D001792:Blood Platelets / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000503:physiopathology; D013927:Thrombosis / Q000209:etiology* / Q000503:physiopathology
D001779:Blood Coagulation Factors