Overview

This book entitled 'STUDIES ON APOLIPOPROTEIN-E GENE TRANSFER TO SKELETAL MUSCLE CELLS IN VITRO AND IN VIVO' is essentially a product of extensive lab-based research. Atherosclerosis results in myocardial and cerebral infarction, aortic aneurysm and peripheral vascular disease. Apolipoprotein E (apoE) protects against atherosclerosis for e.g by sequestering excess cholesterol from vessel walls and having antioxidant/anti-inflammatory actions. Our aim was to test the original hypothesis that expression of apoE from ectopic muscle sites has therapeutic potential to prevent or regress plaque formation, limiting the progression of atherosclerosis. We used plasmid and recombinant adeno-associated viral (rAAV) vectors to express ectopically the 3 human apoE allelic isoforms ( 2, 3 and 4) in muscles of apoE-/- mice, as a preclinical gene therapy model of spontaneous atherosclerosis. The end-point pathology demonstrated lesion and xanthomata retardation in treated animals. In summary, we have identified potential roles for human apolipoprotein E produced from ectopic muscle sites in aortic lesion retardation and as a valid gene augmentation strategy against atherosclerosis.

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9783639517064

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