PPARα controlling HDL metabolism and atherosclerosis

Low serum high-density lipoprotein (HDL) cholesterol concentrations are a feature of the metabolic syndrome that is increasingly being recognized as an important risk factor for cardiovascular disease. HDL is a key mediator of reverse cholesterol transport (RCT), a pathway transporting cholesterol from extrahepatic cells and tissues to the liver for excretion. HDL metabolism is controlled by the interaction of its protein constituents, the apolipoproteins, such as apoA-I and apoA-II, with different enzymes (LCAT, HL, LPL), transfer proteins (CETP, PLTP,…) and lipoprotein receptors (ABCA-1, SR-BI,…). The level of expression of most of these proteins is partly controlled at the level of transcription by transcription factors, among which are the nuclear receptors. Nuclear receptors are activated by small lipophilic signalling molecules. Among these nuclear receptors, peroxisome proliferator-activated receptors were first identified to play a role in the control of lipid metabolism. In this paper, we will focus on the role of PPARα in HDL metabolism, its molecular action mechanism and its potential as pharmacological targets for future drug discovery.