Hyperhomocysteinemia, vascular pathology, and endothelial dysfunction

Hyperhomocysteinemia has been associated with premature atherothrombotic va scular disease. It is not known whether hyperhomocysteinemia induces a dist inct type of vascular disease. Its interaction, if any, with traditional ri sk factors also remains unclear. The pathophysiological mechanisms linking hyperhomocysteinemia to vascular disease have been extensively studied in v itro and in animals. From these studies, it has been suggested that homocys teine limits the bioavailability of nitric oxide (NO), increases oxidative stress, stimulates smooth cell proliferation, and alters elastic wall prope rties. The relevance of these proposed mechanisms in vivo is unclear, becau se clinical studies have yielded controversial results with regard to the r elation between plasma homocysteine levels and indices of endothelial funct ion, such as brachial artery flow-mediated vasodilatation and plasma levels of endothelium-derived marker proteins. Up till now, there have been no co ntrolled 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.