ABSTRACT
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.
KEYWORD
Hyperhomocysteinemia - vascular dis- eases - endothelial function - treatment - athero-thrombosis
