Oxidation of beta-very low density lipoprotein by endothelial cells enhances its metabolism by smooth muscle cells in culture.
We have previously shown that beta-very low density lipoprotein (beta-VLDL) incubated with bovine aortic endothelial cells (ECs) is bound and internalized more readily by cultured rabbit aortic smooth muscle cells (SMCs) than is beta-VLDL incubated in the absence of ECs, resulting in enhanced accumulation of cholesterol. To investigate the mechanism by which this occurs, beta-VLDL from hypercholesterolemic rabbit serum was incubated with cultured bovine aortic ECs. This resulted in the formation of thiobarbituric acid (TBA)-reactive material indicating extensive lipid peroxidation. The formation of TBA-reactive material, the increased metabolism of beta-VLDL by rabbit aortic SMCs, and the increased accumulation of cholesterol were prevented by superoxide dismutase, EDTA, several antioxidants, and, to a lesser extent, by 5,8,11,14-eicosatetraynoic acid, but not by acetylsalicylic acid, suggesting that potential oxidizing agents were the superoxide anion, metal ions, and lipoxygenase derivatives, but not cyclooxygenase derivatives. The percentage composition of phospholipid, protein, triglyceride, and free and esterified cholesterol of EC-modified beta-VLDL did not differ significantly from the unmodified lipoprotein. Displacement studies showed that only part of the interaction of both EC-beta-VLDL and unmodified beta-VLDL occurred through the B/E receptor and that the EC-beta-VLDL displaced 125I-beta-VLDL to a greater extent than did unmodified beta-VLDL. This indicated that the EC-beta-VLDL interacted more strongly with receptors on SMCs.
Horrigan
S
S
Cell Biology Laboratory, Baker Medical Research Institute, Prahran, Australia.
Campbell
J H
JH
Campbell
G R
GR
D000818:Animals; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D011341:Probucol / Q000494:pharmacology; D011817:Rabbits; D013482:Superoxide Dismutase; D014810:Vitamin E / Q000494:pharmacology
D008079:Lipoproteins, VLDL; D014810:Vitamin E; D002084:Butylated Hydroxytoluene; D002784:Cholesterol; D004492:Edetic Acid; D013482:Superoxide Dismutase; D011341:Probucol