Effects of oxidized low density lipoproteins on arachidonic acid metabolism in smooth muscle cells.

The role of oxidized plasma lipoproteins in modify- ing arachidonic acid (AA) metabolism was studied in smooth muscle cells (SMC). Very low density lipoproteins (VLDL), un- oxidized low density lipoproteins (LDLBHT) isolated with buty- lated hydroxytoluene (BHT), and oxidized LDL (LDLoxID) were separated from human serum. Thiobarbituric acid reac- phospholipid synthesize prostanoids and lipid peroxides. L~~ concentrations of prostanoids cell prolifer- ation whereas lipid peroxides and high concentrations of prostanoids inhibit cell proliferation. The effects of fatty acids on the aorta smooth muscle cell (SMC) have been tant (TBAR) levels were adjusted by saline incubations. Prosta- noids in guinea pig SMC cultures were measured either by ra- dioimmunoassay (RIA) or the isolation by high performance liquid chromatography (HPLC) of labeled prostanoids from SMC prelabeled with ( "C)AA. Cell morphology and viability were studied by staining with Giemsa, nile red, and propidium iodide. VLDL and LDLBHT had little effect on prostanoid syn- thesis. Low-TBAR-LDLo~~D enhanced total prostanoid levels and diminished the release of labeled prostanoids. Similar effects were found with exogenous free AA (unlabeled). Low-TBAR- LDLOXID did not affect the release of endogenous phospholipid AA as free AA. Synergism ocurred between LDLOXID and ex- ogenous free AA in prostanoid synthesis. LOW-TBAR-LDLoxID evidently enhanced prostanoid levels in SMC both by supplying AA and by stimulating cyclooxygenase. High-TBAR-LDLoxID blocked prostanoid synthesis and enhanced cell death but time and pulse-recovery experiments showed that these effects were unrelated, High-TBAR-LDLoxID stimulated prostanoid synthe- sis when BHT was added to the incubation media. High-TBAR- LDLXID also caused massive free AA release and the forma- tion of many nonprostanoid derivatives. High-TBAR-LDLxID evidently diminished overall prostanoid levels in SMC by in- hibiting cyclooxygenase and at the same time stimulating AA release and the formation of other AA derivatives. --hang, H., W. B. Davis, X. Chen, K. H. Jones, R. L. Whisler, and D. G. Cornwell. Effects of oxidized low density lipoproteins on arachidonic acid metabolism in smooth muscle cells. J. Lipid &. 1990. 31: 551-565.