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Endothelial marker proteins in hyperhomocysteinemia
S C de Jong1, C D Stehouwer, M van den Berg
1Institute for Cardiovascular Research, Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands.
Insights
High homocysteine levels (hyperhomocysteinemia) may damage blood vessels, but this study found no independent link to endothelial dysfunction markers in healthy individuals. However, elevated von Willebrand factor was noted in hyperhomocysteinemic patients.
Area of Science:
- Cardiovascular Medicine
- Vascular Biology
- Biochemistry
Background:
- Hyperhomocysteinemia is linked to atherosclerosis and thromboembolism, but the underlying mechanisms are unclear.
- Endothelial injury is a proposed mechanism, yet the independent association between hyperhomocysteinemia and endothelial function remains unknown.
- This study investigates endothelial function markers in relation to hyperhomocysteinemia in both healthy individuals and patients with peripheral arterial occlusive disease.
Purpose of the Study:
- To determine if plasma protein markers of endothelial function differ between individuals with and without hyperhomocysteinemia.
- To assess the independent association of hyperhomocysteinemia with endothelial dysfunction.
- To compare endothelial markers in patients with peripheral arterial occlusive disease and healthy controls, with and without hyperhomocysteinemia.
Main Methods:
- Studied 80 individuals under 56 years: 40 healthy, 40 with peripheral arterial occlusive disease, divided by homocysteine levels.
- Measured plasma levels of endothelium-derived proteins: von Willebrand factor (vWf), vWf propeptide (vWf: AgII), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), cellular fibronectin (cFN), and thrombomodulin (TM).
- Assessed C-reactive protein (CRP) as an inflammatory marker.
Main Results:
- Patients with peripheral arterial occlusive disease showed significantly higher levels of vWf, vWf: AgII, tPA, and CRP compared to healthy individuals.
- No significant differences in most marker protein levels were found between hyperhomocysteinemic and normohomocysteinemic individuals.
- A notable exception was significantly elevated vWf in hyperhomocysteinemic patients compared to normohomocysteinemic patients.
Conclusions:
- Peripheral arterial occlusive disease is associated with markers of endothelial activation and inflammation.
- Hyperhomocysteinemia was not independently associated with altered endothelial cell function markers in healthy subjects.
- While vWf was elevated in hyperhomocysteinemic patients, overall evidence for an independent link between hyperhomocysteinemia and endothelial dysfunction markers in this cohort was not found.
Abstract:
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: AgII), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), cellular fibronectin (cFN) and thrombomodulin (TM). In addition we assessed C-reactive protein (CRP). vWf, vWf: AgII, 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.