Regulation of high density lipoprotein binding activity of aortic endothelial cells by treatment with acetylated low density lipoprotein.
High density lipoprotein (HDL) binding to human fibroblasts and arterial smooth muscle cells is up-regulated when sterol is delivered to cells in the form of nonlipoprotein cholesterol or low density lipoprotein (LDL). Results from the present study show that the HDL binding activity of aortic endothelial cells is up-regulated when cholesterol in the form of acetylated LDL (AcLDL) is delivered to cells via the "scavenger" lipoprotein receptor pathway. AcLDL treatment led to a dose-dependent, but saturable, increase in HDL binding to cultured bovine aortic endothelial cells that was reversed when cells were treated with lipoprotein-deficient serum. The AcLDL-mediated enhancement in HDL binding activity was inhibited by cycloheximide, suggesting the involvement of protein synthesis. This enhancement was associated with an increased cell cholesterol content, a suppressed rate of cholesterol synthesis, and an increased rate of cholesterol ester formation. Kinetic analysis of HDL binding showed that AcLDL treatment caused an increase in the apparent number of high-affinity binding sites (Kd approximately 3 micrograms/ml HDL protein). Competition and direct binding studies revealed that the inducible binding sites exhibited relative specificity for HDL over LDL and AcLDL. Thus, aortic endothelial cells appear to possess specific receptors for HDL that may function to facilitate HDL-mediated removal from cells of excess cholesterol internalized by the scavenger receptor pathway.
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000378:metabolism
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C032629:acetyl-LDL