[The role of transmembrane lipidtransporter molecules in the atherosclerotic process]

The role of transmembrane lipidtransporter molecules in the atherosclerotic process. The protective effect of high-density lipoprotein in the atherosclerotic process has been mainly attributed to its role in reverse cholesterol transport. Identification of mutations in the ATP-bindig casette transporter-A1 (ABCA1) as the genetic defect in genetic high-density lipoprotein-deficiency (Tangier disease) and selected patients with familiar hypoalphalipoproteinemia has generated interest in discovering the role of this lipid transporter molecule in the reverse cholesterol transport. It is well established, that the ABCA1 mediates cellular cholesterol efflux through transfer of phospholipids and cholesterol from the inner to the outer layer of the cell membrane, thus enabling the bindig to apolipoproteins. Previous studies showed that the ABCA1 is critically involved in cellular trafficking of cholesterol and phospholipids in total body of lipid homeostasis. In Tangier disease, the loss of the function of ABCA1, leads to an impaired formation of nascent high-density lipoprotein particles by preventing the release of cellular phospholipids and cholesterol to the acceptor apolipoprotein A1. This rare genetic disorder is characterized by a severe high-density lipoprotein deficiency, cholesterol deposition in macrophages and premature atherosclerosis. These findings implicate the ABCA1 as an important therapeutic target for preventing diseases that are associated with accelerated atherogenesis. The present review summarizes the current knowledge of the ABCA1, its pivotal role in the cholesterol homeostasis and preventing atherosclerosis.