HDL Elevation and Lipid Lowering Therapy: Current Scenario and Future Perspectives

High density lipoprotein (HDL) has proven its role in reverse cholesterol transport and cellular cholesterol efflux thus acting as a protective factor against atherogenic cardiovascular diseases. The article focuses primarily on structure and function of genes influencing HDL metabolism. Various novel targets involve liver X receptor, retinoid X receptor and peroxisome proliferators activated receptor agonists and apoA-I mimetics. New molecules targeting these receptors are described. Phospholipid transfer protein and scavenger receptor B1 are also attractive targets in HDL metabolism. ATP-Binding Cassette transporter A1 and several lipases also play a crucial role in HDL metabolism and are very useful target for atherogenic dyslipidemia. Several cholesterol ester transfer protein inhibitors have shown great promise as possible drug candidates of future. Notably, JTT-705 (Japan Tobacco, Roche) is of great interest in spite of withdrawal of torcetrapib. Considering modest effect of currently available therapeutic options on HDL, these novel HDL elevating targets are doubtlessly the target for future atherosclerotic intervention.

Keywords: HDL elevation, coronary artery disease, ATP-binding cassette transporter A1, liver X receptor, retinoid X receptor, peroxisome proliferators activated receptor, phospholipids transfer protein, scavenger receptor B1, lipoprotein lipase, hepatic lipase, endothelial lipase, cholesteryl ester transfer protein, apolipoprotein A-I