Figure 1.

Triglyceride-rich lipoprotein metabolism and mechanism of atherosclerosis. TGRLs are derived from an endogenous pathway through the liver and an exogenous pathway through the small intestine. In the endogenous pathway, VLDL is produced in the hepatocytes from FFAs derived from the circulation or newly synthesized in the liver. A variety of apolipoproteins are added to the surface of the nascent VLDL particle during secretion, including apoB100, apoCII, apoCIII, and apoE. Once VLDL is secreted into the plasma, LPL along the luminal surface of capillaries hydrolyzes the TGs within the core of VLDL into FFAs generating VLDL remnant/IDL particles and lipolytic products. The FFAs are taken up by muscle and adipose tissue. The IDL particles are further catabolized into LDL and lipolytic products by HL. In the exogenous pathway, dietary fats are absorbed by enterocytes and incorporated into apoB48 containing chylomicrons, which are then secreted into the lymphatic system and enter the circulation, where they acquire apoCII, apoCIII, and apoE. In the circulation, LPL along the luminal surface of capillaries hydrolyzes the TGs within the core of chylomicrons into FFAs generating chylomicron remnant particles. The FFAs can be taken up muscle and adipose tissue. Endogenous and exogenous remnants are cleared from the circulation by hepatic uptake via the LDL receptor, LRP1, and HSPG receptor. LPL plays a key role in TGRL metabolism and is highly regulated by various proteins. ANGPTL 3, ANGPTL 4, and apoCIII inhibit LPL activity, whereas apoCII is an important activator of LPL activity. TGRL and their remnants readily penetrate the arterial wall and can be taken up by scavenger receptors on macrophages directly without oxidative modification, leading to formation of foam cells and atherosclerotic plaque development. ANGPTL, angiopoietin-like protein; HL, hepatic lipase; LRP1, LDL receptor related protein-1; HSPG, heparan sulfate proteoglycan.