Figure 1

Intestinal and liver β-lipoprotein synthesis and vascular modification. Ingested lipids are hydrolyzed in the lumen of the intestine to absorbable species, such as free cholesterol, free fatty acids, and monoacylglycerol. These molecules are re-esterified in the enterocyte of the small intestine to triacylglycerol (TG), cholesteryl esters (CE), and phospholipids (not shown) and packaged into chylomicrons, whose signature coat protein in humans is Apob48 (one molecule per particle). This particle enters the vasculature and acquires an Apoc2 molecule from an HDL particle (not shown). Apoc2 is a required binding partner for lipoprotein lipase (LPL), an enzyme tethered to the apical surface of capillary bed endothelial cells in muscle and adipose tissues (20). LPL liberates free fatty acids for use by these tissues. The partially lipid-depleted chylomicron remnant is rapidly cleared by the liver through the action of Apoe-binding LRP receptors and Apob-binding low-density lipoprotein receptors (LDLR). The liver synthesizes very low-density lipoprotein (VLDL) particles from de novo lipogenesis-derived fatty acids and re-esterified fatty acids that reach the liver after adipocyte hydrolysis (and has relatively less CE in it). Human VLDL’s signature coat protein is Apob100. Following LPL-catalyzed lipid hydrolysis, VLDL remnants, intermediate density lipoprotein (IDL) particles, are either rapidly cleared by the liver or mature into LDL. LDL particles have a long circulating half-life, and they can deposit under vascular endothelial cells, undergo oxidation, and trigger an inflammatory atherosclerotic reaction with subsequent plaque rupture and thrombosis causing ischemia to the supplied tissue.