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Project

The role of homocysteine in atherothrombosis revisited.

Hyperhomocysteinemia is a metabolic risk factor for ischemic cardiovascular diseases. The 'homocysteine hypothesis' argues that a causal relationfhips exists between homocysteine levels and the occurrence of atherosclerotic vascular diseases. However, clinical trials have hitherto not been able to prove this hypothesis. This may be attributable to the limited efficacy and low selectivity of the selected interventions (vitamin B6, vitamin B12, folic acid supplements). On the other hand, the 'homocysteine hypothesis' may be incorrect and the observed epidemiological relationship may rely on the presence of confounding variables. This project utilizes hepatocye-specific gene transfer to selectively lower plasma homocysteine and/or plasma cholesterol levels. The primary objective of this project is the re-evaluation of the 'homocysteine hypothesis' and, more specifically, to test the hypothesis that a threshold exists in the relationship between plasma homocysteine levels and atherogenesis in a mouse model of combined hyperhomocysteinemia and hypercholesterolemia. In addition, this model will also be used to assess the value of endothelial progenitor cell (EPC) number, EPC function and endothelial function as predictors of the progression of atherosclerosis. The second objective of these studies is to evaluate whether the increase in EPC number and EPC function following selective lowering of plasma homocysteine and/or plasma cholesterol levels in a combined model of hyperhomocysteinemia and hypercholesterolemia results in increased survival and improved ventricular remodelling post-myocardial infarction.
Date:1 Oct 2009 →  29 Feb 2012
Keywords:Endothelial progenitor cells, Cardiac remodeling, Gene transfer, Homocysteine, Atherosclerosis, Myocardial infarction, Ischemic cardiovascular diseases
Disciplines:Cardiac and vascular medicine