Stimulation of reverse cholesterol by somatic gene transfer

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Project objective

Research objectives and content There is an inverse correlation between incidence of atherosclerosis and the HDL levels. This protective activity of HDL is generally attributed to its role in the reverse, cholesterol transport, mechanism by which peripheral cells transport cholesterol excess to the liver to elimination through the bile. And so, reverse cholesterol transport seem to be a good potential therapeutic target for treating atherosclerosis. In the project, we want to enhance reverse cholesterol transport using somatic gene transfer by overexpression of apoA-I (the major protein of the HDL) in the liver and validate reverse cholesterol transport as a therapeutic target in gene-therapy for atherosclerosis. This will be made after construction of plasmid and adenoviral vectors with gene insert of apoA-I, and transfection into cultured cells or atherosclerotic animal models. We will follow apoA-I concentration and expression level of apoA-I gene to verify the overexpression expected. Then, we will look for the impact of this overexpression at the metabolic and physiological levels. Transfected cells and animals will be used for cellular cholesterol efflux measurements. The lipoprotein profile, LCAT activity (and biliary secretion of cholesterol for the animals) will be studied on these models, accompanied by a physiological study of the atherosclerosis development on the animals. Training content (objective, benefit and expected impact) This project will allow us to validate reverse cholesterol transport as therapeutic target in gene-therapy for atherosclerosis.

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Participants

• Aristotle University of Thessaloniki · ThessalonikiCoordinatorGreece

Links

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