Hepatic heparan sulfate proteoglycans and endocytic clearance of triglyceride-rich lipoproteins

Abstract

Hypertriglyceridemia, characterized by the accumulation of triglyceride-rich lipoproteins in the blood, affects 10-20% of the population in western countries and increases the risk of atherosclerosis, coronary artery disease, and pancreatitis. The etiology of hypertriglyceridemia is complex, and much interest exists in identifying and characterizing the biological and environmental factors that affect the synthesis and turnover of plasma triglycerides. Genetic studies in mice have recently identified that heparan sulfate proteoglycans are a class of receptors that mediate the clearance of triglyceride-rich lipoproteins in the liver. Heparan sulfate proteoglycans are expressed by endothelial cells that line the hepatic sinusoids and the underlying hepatocytes, and are present in the perisinusoidal space (space of Disse). This chapter discusses the dependence of lipoprotein binding on heparan sulfate structure and the identification of hepatocyte syndecan-1 as the primary proteoglycan that mediates triglyceride-rich lipoprotein clearance.