Lipoprotein-induced prostacyclin production in endothelial cells and effects of lipoprotein modification
Myers, D.E.; Huang, W.N.; Larkins, R.G.
American Journal of Physiology 271(5 Pt 1): C1504-C1511
1996
ISSN/ISBN: 0002-9513 PMID: 8944633 Document Number: 456547
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 (PGI-2) production by bovine aortic endothelial cells (BAEC). Modified low-density lipoprotein (LDL) increased PGI-2 production in the short term (up to 24 h), but oxidized LDL caused an inhibition of PGI-2-producing capacity in longer term incubations (48-72 h). Glycated (Glc) high-density lipoprotein 3 (HDL-3) caused higher production of PGI-2 in the short term (4-24 h) but reached similar levels as HDL-3 over time. Glycation of high-density lipoprotein 2 had no effect on the PGI-2-producing capacity of the lipoprotein. Thus modification of the lipoproteins affects their potential to induce PGI-2 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 PGI-2 production, may be involved in compromised endothelial function, since GlcLDL is prone to oxidation.