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]F-1 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-PGF(1 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 mu mol/L) or vitamin E (100 mu mol/L), basal and bradykinin-stimulated formation of 6-keto-PGF(1 alpha) was potentiated by 20 mu g protein/mL of LDL. Ox-LDL decreased unstimulated formation of the eicosanoid from 3.1+/-0.2 pg/mu g protein in control cells to 1.6+/-0.1 and 0.5+/-0.1 pg/mu g protein after 3-day incubation with 5 and 20 mu g protein/mL of Ox-LDL, respectively (P<.05). As in the basal state, Ox-LDL decreased bradykinin-induced 6-keto-PGF(1 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 mu g protein/mL of either LDL or Ox-LDL. However, no change was apparent in the bradykinin (10 mu mol/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. This phenomenon could be involved in the progression of the fatty streak to a more advanced lesion. (Arterioscler Thromb. 1994;14:453-459.)