Oxidized lipoprotein autoimmunity: an emerging drug target in cardiovascular disease

Oxidative modification of low-density lipoprotein (LDL) in the arterial wall is believed to be one of the most important mechanisms involved in the development of atherosclerosis. It is well established that oxidized (Ox)-LDL uptake is responsible for the formation of macrophage foam cells, one of the most characteristic hallmarks of the atherosclerotic plaque, and that the proinflammatory and cytotoxic effects of Ox-LDL play an important role in vascular inflammation and lesion development. More recently, it has become apparent that Ox-LDL is also recognized by the immune system, thus resulting in innate and adaptive immune reactions modulating both Ox-LDL clearance and the vascular inflammatory response. The finding that some of these immune responses have a protective effect against plaque development has focused attention on the potential to develop novel therapies for the prevention and treatment of cardiovascular disease based on the selective activation of this protective immunity by vaccines, or mimicking them directly by using Ox-LDL-specific antibodies.