Receptor-dependent uptake of human chylomicron remnants by cultured skin fibroblasts.
Human chylomicrons were isolated from plasma from a subject with familial hypertriglyceridemia and converted to chylomicron remnants by incubation with postheparin plasma. The interaction of these apolipoprotein E-containing, cholesterol-rich human chylomicron remnants with cultured skin fibroblasts was studied. Chylomicron remnants were internalized by skin fibroblasts as a unit, mainly via the low density lipoprotein (LDL)-receptor pathway, resulting in increased cell cholesterol content. After entering the fibroblast, chylomicron remnants stimulated cholesterol esterification, suppressed 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, and down-regulated LDL receptor activity similar to the action of LDL. As a function of increasing lipolysis, remnant particles were progressively more effectively taken up by skin fibroblasts, despite a decrease in the apolipoprotein E content per lipoprotein particle. Remnant particles produced after hydrolysis of 70 to 80% of chylomicron triglyceride increased cell cholesterol content to an amount nearly identical to that observed with LDL when the two lipoproteins were incubated at an equal cholesterol concentration. However, when incubated on the basis of equal particle number, chylomicron remnants were 2 to 3 times more effective than LDL in delivering cholesterol to the cells. These results suggest that chylomicron remnants play a role in the regulation of postabsorptive cholesterol homeostasis in nonhepatic cells, and possibly in the pathogenesis of atherosclerosis.
D001692:Biological Transport; D002478:Cells, Cultured; D002784:Cholesterol / Q000032:analysis; D002788:Cholesterol Esters / Q000032:analysis; D002914:Chylomicrons / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000378:metabolism; D007700:Kinetics; D010743:Phospholipids / Q000032:analysis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D012867:Skin / Q000378:metabolism*; D014280:Triglycerides / Q000032:analysis
D002788:Cholesterol Esters; D002914:Chylomicrons; D010743:Phospholipids; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; D014280:Triglycerides; C028203:chylomicron receptor; D002784:Cholesterol