Reverse cholesterol transport, high density lipoproteins and HDL cholesterol: recent data

Unlike LDL cholesterol, which is a major cardiovascular risk factor, HDL cholesterol plays an important anti-atherogenic role through reverse cholesterol transport from peripheral cells to the liver. Some recent biochemical and epidemiological data shed light on this key function. In the hereditary Tangier disease with disseminated lipid storage, the main biochemical feature is a dramatically low level of HDL cholesterol. Different mutations in the ATP-binding cassette transporter A1 (ABCA1) gene have been recently described, which interfere with cellular cholesterol efflux. This results in low HDL plasma level, and defective reverse cholesterol transport to the liver. Moreover, selective hepatic uptake of HDL cholesteryl esters by SR-B1, a class B scavenger receptor, also plays a key role. In the follow-up of the PROCAM Study, the relative risk of coronary events is high in a cluster of patients with increased total cholesterol/HDL-cholesterol ratio. In the prospective secondary prevention VA-HIT study, the relative risk of coronary events in patients with low HDL cholesterol levels is decreased of 22% with a treatment by gemfibrozil. If the present available range of drugs targeted at increasing HDL cholesterol levels is rather narrow, future therapies will be encouraging, especially with agonists of PPARs.