Hyperhomocysteinemia, vascular pathology, and endothelial dysfunction.
Hyperhomocysteinemia has been associated with premature atherothrombotic vascular disease. It is not known whether hyperhomocysteinemia induces a distinct type of vascular disease. Its interaction, if any, with traditional risk factors also remains unclear. The pathophysiological mechanisms linking hyperhomocysteinemia to vascular disease have been extensively studied in vitro and in animals. From these studies, it has been suggested that homocysteine limits the bioavailability of nitric oxide (NO), increases oxidative stress, stimulates smooth cell proliferation, and alters elastic wall properties. The relevance of these proposed mechanisms in vivo is unclear, because clinical studies have yielded controversial results with regard to the relation between plasma homocysteine levels and indices of endothelial function, such as brachial artery flow-mediated vasodilatation and plasma levels of endothelium-derived marker proteins. Up till now, there have been no controlled data on the effects of homocysteine-lowering treatment on vascular function or clinical end points. The precise mechanisms (if any) by which homocysteine mediates its adverse vascular effects are in fact unknown but may relate to impaired endothelial and smooth muscle cell function.
van Guldener
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Department of Internal Medicine, University Hospital and Institute for Cardiovascular Research Vrije Universiteit, Amsterdam, The Netherlands. CDA.stehouwer@azvu.nl
Stehouwer
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D000328:Adult; D000818:Animals; D001161:Arteriosclerosis / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D015415:Biomarkers; D001808:Blood Vessels / Q000473:pathology*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D016893:Carotid Stenosis / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D002648:Child; D015897:Comorbidity; D017023:Coronary Angiography; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006712:Homocystinuria / Q000097:blood / Q000150:complications / Q000235:genetics; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications* / Q000473:pathology; D006965:Hyperplasia; D006973:Hypertension / Q000453:epidemiology; D007676:Kidney Failure, Chronic / Q000097:blood; D008297:Male; D008715:Methionine / Q000494:pharmacology / Q000633:toxicity; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D015995:Prevalence; D011817:Rabbits; D051381:Rats; D014664:Vasodilation
D015415:Biomarkers; D009569:Nitric Oxide; D008715:Methionine