Chronic exposure of cultured bovine endothelial cells to oxidized LDL abolishes prostacyclin release.
We investigated the effect of chronic exposure (3 days) with low-density lipoprotein (LDL) and oxidized (Ox)-LDL on the unstimulated and stimulated formation of prostacyclin (6-keto-prostaglandin [PG]F1 alpha) and total inositol phosphates (IPs) by cultured bovine aortic endothelial cells. Neither basal nor bradykinin-stimulated (1 to 10 nmol/L) formation of 6-keto-PGF1 alpha was affected by LDL, except at the highest concentration of bradykinin tested (100 nmol/L). In the presence of the antioxidants N-acetyl-L-cysteine (NAC, 10 mumol/L) or vitamin E (100 mumol/L), basal and bradykinin-stimulated formation of 6-keto-PGF1 alpha was potentiated by 20 micrograms protein/mL of LDL. Ox-LDL decreased unstimulated formation of the eicosanoid from 3.1 +/- 0.2 pg/micrograms protein in control cells to 1.6 +/- 0.1 and 0.5 +/- 0.1 pg/microgram protein after 3-day incubation with 5 and 20 micrograms protein/mL of Ox-LDL, respectively (P < .05). As in the basal state, Ox-LDL decreased bradykinin-induced 6-keto-PGF1 alpha formation. NAC or vitamin E did not influence Ox-LDL-induced endothelial cell changes in eicosanoid production. IPs formation by endothelial cells increased to a similar extent in the presence of 20 micrograms protein/mL of either LDL or Ox-LDL. However, no change was apparent in the bradykinin (10 mumol/L)-induced increase in total IPs formation after incubation with the lipoproteins. The data indicate that chronic exposure to Ox-LDL abolishes the production of prostacyclin by cultured endothelial cells. The oxidatively modified lipoprotein seems to more specifically affect the prostacyclin pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
Thorin
E
E
University of Glasgow, Department of Medicine and Therapeutics, Western Infirmary, UK.
Hamilton
C A
CA
Dominiczak
M H
MH
Reid
J L
JL
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D006868:Hydrolysis; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010716:Phosphatidylinositols / Q000378:metabolism; D011506:Proteins / Q000032:analysis
D008077:Lipoproteins, LDL; D010716:Phosphatidylinositols; D011506:Proteins; D011464:Epoprostenol; D001920:Bradykinin