부산대학교 도서관

Elevated plasma cholesterol associated with low-density lipoproteins (LDL) is a well-established factor in the development of cardiovascular diseases. The LDL receptor is central to our understanding of LDL clearance from the plasma compartment and emerging evidence suggests that hepatic overproduction of very low-density lipoproteins (VLDL) is also an important contributor to metabolic dyslipidemic states with increased cardiovascular disease risk. Intracellular degradation of newly synthesized apolipoprotein (Apo)B protein can regulate the rate of hepatic VLDL secretion by disrupting the assembly of ApoB into VLDL. In diabetes and insulin resistance, disruption of the normal insulin signaling pathways can also result in increased hepatic VLDL secretion, in part, by altering ApoB degradation. Current pharmaceutical approaches to lower plasma LDL mostly target lipid biosynthetic and transfer pathways necessary for the hepatic assembly of VLDL. However, recent advances in the mechanisms of VLDL assembly and ApoB degradation may lead to new approaches to reduce the production of hepatic VLDL. This review highlights new developments and current views on cellular and molecular mechanisms of VLDL production by the liver, and considers new therapeutic approaches to reduce hepatic VLDL secretion.