Lipoprotein-induced prostacyclin production in endothelial cells and effects of lipoprotein modification.
Although lipoprotein modification has been implicated in atherogenesis, the effect of modified forms of lipoproteins on vascular cell function has not been fully resolved. We have investigated lipoprotein-induced prostaglandin production by macrovascular endothelial cells. This study delineates early responses of endothelial cells after exposure to native and modified forms of the lipoproteins. Modification of lipoproteins by oxidation or glycation significantly affected the capacity of lipoproteins to induce prostacyclin (PGI2) production by bovine aortic endothelial cells (BAEC). Modified low-density lipoprotein (LDL) increased PGI2 production in the short term (up to 24 h), but oxidized LDL caused an inhibition of PGI2-producing capacity in longer term incubations (48-72 h). Glycated (Glc) high-density lipoprotein 3 (HDL3) caused higher production of PGI2 in the short term (4-24 h) but reached similar levels as HDL3 over time. Glycation of high-density lipoprotein 2 had no effect on the PGI2-producing capacity of the lipoprotein. Thus modification of the lipoproteins affects their potential to induce PGI2 production in endothelial cells, and this may have an influence on vascular function in disease states such as diabetes and atherosclerosis. Although the changes appear to contradict data from long-term in vivo studies, these results from in vitro studies may reflect the situation in very early lesion development. GlcLDL, while causing an increase in endothelial cell PGI2 production, may be involved in compromised endothelial function, since GlcLDL is prone to oxidation.
Myers
D E
DE
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Huang
W N
WN
Larkins
R G
RG
D000704:Analysis of Variance; D000818:Animals; D001011:Aorta; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D017127:Glycation End Products, Advanced; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008315:Malondialdehyde / Q000032:analysis; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D000093844:Glycated Proteins
D011464:Epoprostenol; D017127:Glycation End Products, Advanced; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008315:Malondialdehyde; D017392:Thiobarbituric Acid Reactive Substances; C031797:glycated lipoproteins, LDL; D000093844:Glycated Proteins; C099252:oxidized low density lipoprotein