High-density lipoprotein: gene-based approaches to the prevention of atherosclerosis

Although the atheroprotective role of high-density lipoprotein (HDL) has be en well documented in epidemiological and animal studies, highly effective therapeutic approaches for the selective increase of plasma HDL levels or f unction are not yet available. Several mechanisms by which HDL exerts an at heroprotective effect have been proposed on the basis of experiments in vit ro and in vivo. These mechanisms include directing excess cellular choleste rol from the peripheral tissues to the liver in 'reverse cholesterol transp ort', inhibiting oxidative modification or aggregation of LDL, and modulati ng inflammatory responses to favour vasoprotection. This review gives an ov erview of the genes regulating these mechanisms, such as those encoding apo lipoprotein AT, lecithin:cholesterol acyltransferase (LCAT), scavenger rece ptor B1 (SR-BI), and the ATP-binding cassette transporter 1 (ABC1), and the potential to exploit them to develop gene-based therapeutic approaches to increase the level or function of HDL.