GENE-THERAPY FOR THE VULNERABLE PLAQUE

Acute coronary events result from the rupture of an atherosclerotic plaque, leading to formation of an occlusive coronary thrombus. Recent developments in the field of gene transfer provide the opportunity to genetically modify cells involved in plaque rupture as well as thrombus formation and thus prevent acute coronary syndromes. A first approach consists of transferring genes, the product of which may stabilize the vulnerable plaque by reducing the plaque content in lipids and macrophages. Alternatively, the introduction into the atherosclerotic plaque of genes encoding for thrombolytic proteins or growth factors able to restore physiologic antithrombotic functions of endothelial cells may inhibit thrombus formation should the plaque rupture. The success of such strategies depends on the efficiency with which the transgene is introduced and expressed into the target cell, the duration of transgene expression and the ability of the transgene product to ultimately prevent plaque rupture or thrombus formation, or both.