A genome-wide sirna screen as a tool to unveil new players in hepatic high density lipoprotein and low density lipoprotein metabolism

Aim: Plasma levels of high density lipoproteins (HDL)-associated cholesterol are inversely associated with cardiovascular disease. Out of the many mechanisms that have been proposed to explain this association, the best described one is the ability of HDL to extract cholesterol from peripheral tissues and to deliver it to the liver for biliary excretion. Part of the delivery of cholesterol to the hepatocyte is made possible by the Scavenger Receptor B1 through selective cholesterol uptake (SCU). In addition to SCU and similar to LDL, some HDL particles are endocytosed by hepatocytes as whole particles (holoparticle uptake). The mechanisms of HDL holoparticle uptake are little understood.