Role of the Endothelium in Lipoprotein Metabolism

Abstract

For a long time the endothelium was considered as a passive exchange barrier of lipoproteins between plasma and extravascular tissues. During the past two decades many data from clinical studies, cell culture, and animal experiments have shown that endothelial cells are a target of physiological and pathological actions of lipoproteins: Whereas lysosphingolipids and apolipoprotein (apo)A-I in native high-density lipoproteins (HDL) exert protective effects on the integrity and function of endothelial cells, modified low-density lipoproteins (LDL) and remnants of lipoproteins tend to disturb endothelial function. One central function of the endothelium is the control of protein trafficking between intravascular and extravascular compartments. Both LDL and HDL can pass the intact endothelium through transcytosis by processes which involve caveolin-1 and the LDL-receptor (for LDL) or ATP-binding cassette (ABC) transporters and scavenger receptor (SR)-BI for apoA-I and HDL, respectively. Finally the endothelium has evolved as a regulator of lipoprotein metabolism: By expressing or presenting lipases [lipoprotein lipase (LPL), hepatic lipase (HL), endothelial lipase (EL)] as well as LPL-receptors (glycerophosphatidyl inositol anchored HDL binding protein 1; GPIHBP1) the endothelium contributes to the remodelling of all lipoprotein classes. Selective conditional knock-outs of widely expressed genes like peroxisome proliferator agent receptor gamma (PPARγ) in mice are starting to reveal additional specific effects of the endothelium on lipid and lipoprotein metabolism.