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

H. Zhang, W. B. Davis, X. Chen, K. H. Jones, R. L. Whisler, D. G. Cornwell

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The role of oxidized plasma lipoproteins in modifying arachidomic acid (AA) metabolism was studied in smooth muscle cells (SMC). Very low density lipoproteins (VLDL), unoxidized low density lipoproteins (LDL(BHT)) isolated with butylated hydroxytoluene (BHT), and oxidized LDL (LDL(OXID)) were separated from human serum. Thiobarbituric acid reactant (TBAR) levels were adjusted by saline incubations. Prostanoids in guinea pig SMC cultures were measured either by radioimmunoassay (RIA) or the isolation by high performance liquid chromatography (HPLC) of labeled prostanoids from SMC prelabeled with [14C]AA. Cell morphology and viability were studied by staining with Giemsa, nile red, and propidium iodide. VLDL and LDL(BHT) had little effect on prostanoid synthesis. Low-TBAR-LDL(OXID) enhanced total prostanoid levels and dimished the release of labeled prostanoids. Similar effects were found with exogenous free AA (unlabeled). Low-TBAR-LDL(OXID) did not affect the release of endogenous phospholipid AA as free AA. Synergism occurred between LDL(OXID) and exogenous free AA in prostanoid synthesis. Low-TBAR-LDL(OXID) evidently enhanced prostanoid levels in SMC both by supplying AA and by stimulating cyclooxygenase. High-TBAR-LDL(OXID) blocked prostanoid synthesis and enhanced cell death but time and pulse-recovery experiments showed that these effects were unrelated. High-TBAR-LDL(OXID) stimulated prostanoid synthesis when BHT was added to the incubation media. High-TBAR-LDL(OXID) also caused massive free AA release and the formation of many nonprostanoid derivatives. High-TBAR-LDL(OXID) evidently diminshed overall prostanoid levels in SMC by inhibiting cyclooxygenase and at the same time stimulating AA release and the formation of other AA derivatives.

Original languageEnglish (US)
Pages (from-to)551-565
Number of pages15
JournalJournal of Lipid Research
Volume31
Issue number4
StatePublished - Jan 1 1990

Keywords

  • PGE
  • PGI
  • cyclooxygenase
  • cytotoxicity
  • fatty acid release
  • high performance liquid chromatography
  • radioimmunoassay
  • thiobarbituric acid reactants

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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  • Cite this

    Zhang, H., Davis, W. B., Chen, X., Jones, K. H., Whisler, R. L., & Cornwell, D. G. (1990). Effects of oxidized low density liporoteins on arachidonic acid metabolism in smooth muscle cells. Journal of Lipid Research, 31(4), 551-565.