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Ischemic injury of endothelium, oxidation of LDL and artherothrombosis

Research project P4/34 (Research action P4)

Persons :

Description :

The research project includes 5 sections:

1. In vitro analysis of the effects of oxidised LDL on endothelial and smooth muscle cell function under static and flow conditions, including the interaction between endothelial cells and monocytes, respectively platelets, and the migration and proliferation of smooth muscle cells.

2. Analysis of LDL in vivo oxidation mechanisms and of the effects of oxidised LDL on the progression and thrombogenicity of atherosclerotic lesions in animal models (mice, rabbits, and miniature pigs).

3. Prospective studies to assess the role of oxidised LDL in the development of atherothrombosis in patients.

4. Study of the effects of high HDL levels on arterial stenosis, prevention of atherosclerosis and regression of atherosclerotic lesions in transgenic mice and in mice and miniature pigs treated with recombinant adenoviruses inducing the liver-specific expression of apolipoprotein A-I, the most abundant apolipoprotein of HDL.

5. Study of the correlation between expression of metalloproteinases and specific inhibitors, activation of the fibrinolytic system and progression of atherosclerosis.

An integrated analysis of the mechanisms of atherothrombosis requires molecular- and cell-level in vitro studies, organ-level ex vivo studies, and in vivo studies. The complementarity of the three network partners makes such an integrated approach possible.

The techniques developed by the FUNDP team to study gene regulation can be applied at cell level (FUNDP and UCL) and at organ level (FUNDP and KUL). The in vitro model of the arterial wall (UCL) makes it possible to study the impact of cell interactions on gene expression (UCL and FUNDP) and to reproduce molecular and cellular interactions observed in vivo (UCL and KUL). Animal models are available for experimental intervention studies with a main focus on gene therapy. The close proximity of the University hospital is a major asset for clinical studies.

These studies will contribute significantly to understanding the complex pathogenesis of ischaemic cardiovascular diseases and may thereby open new approaches to diagnosis and treatment.

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