Summary
Hyperhomocysteinemia is associated with severe, premature atherosclerosis and thromboembolism.
The mechanisms involved in the atherogenic and thrombotic complications of hyperhomocysteinemia
are not understood. It has been suggested that hyperhomocysteinemia predisposes to
atherosclerosis by injuring the vascular endothelium. Whether hyperhomocysteinemia
is independently associated with changed endothelial function, either in the absence
or the presence of clinically manifest atherosclerotic disease, is, however, not known.
Therefore we investigated, both in patients with peripheral arterial occlusive disease
and in healthy individuals, whether plasma protein markers of endothelial function
differed between subjects with, and subjects without hyperhomocysteinemia. We studied
80 individuals under the age of 56 years: healthy individuals with (n = 20) and without
(n = 20) hyperhomocysteinemia and patients with peripheral arterial occlusive disease
with (n = 20) and without (n = 20) hyperhomocysteinemia. The following endothelium-derived
proteins were measured as markers of endothelial cell function: von Willebrand factor
(vWf) and von Willebrand factor propeptide (vWf: Agll), tissue-type plasminogen activator
(tPA), plasminogen activator inhibitor-1 (PAI-1), cellular fibronectin (cFN) and thrombomodulin
™. In addition we assessed C-reactive protein (CRP). vWf, vWf: Agll, tPA and CRP were
significantly higher in the patients with peripheral arterial occlusive disease than
in the healthy individuals. No differences in marker protein plasma levels were found
between individuals with, and those without hyperhomocysteinemia, apart from vWf,
which was significantly raised in hyperhomocysteinemic as compared to normohomocysteinemic
patients. We did not find any evidence for an independent association between hyperhomocysteinemia
and protein markers of endothelial cell function in healthy subjects.
