title: Effects of prostaglandins and nitric oxide on rat macrophage lipid metabolism in culture: implications for arterial wall-leukocyte interplay in atherosclerosis.
abstract: Macrophages/foam cells have a pivotal role in atherogenesis although little is known about the way lipid imbalance, a hallmark of atherosclerosis, leads to lipid accumulation in these cells. Modified low-density lipoproteins are associated with macrophage lipid dysfunction in atherosclerosis, but a possible role for altered lipogenesis leading to lipid accumulation remains to be elucidated. Since endothelium-derived nitric oxide (NO) and prostaglandins (PGs) are physiological autacoids whose production may be impaired in atherosclerosis, the effects of these mediators on de novo lipid synthesis in 24-h cultured rat peritoneal macrophages is investigated. In resident (unstimulated) cells, 1 microM PGE2 and the stable analog of PGI2 carbaprostacyclin (cPGI2, 1 microM) deviated the overall [1-14C]acetate from incorporation into cholesterol, free fatty acids and triacylglycerols favoring the formation of phospholipids. In inflammatory (thioglycollate-elicited) macrophages, these eicosanoids likewise reduced 14C-incorporations into all the lipid fractions tested. Also, cPGI2 and PGE2 reduced [4-14C]cholesterol uptake from inflammatory cells but did not interfere in 14C-cholesterol export. The PGE2-derivative PGA2 (10-20 microM) reduced 14C-incorporations into all the lipids in resident cells while it enhanced phospholipid synthesis by up to 129% at the expense of reduced incorporations into the other test lipids. The NO donor S-nitroso-N-acetylpenicillamine (SNAP, 1-10 microM), when added to macrophages in the presence of superoxide dismutase (SOD, to avoid the reaction of superoxide with NO), significantly reduced lipogenesis especially in inflammatory cells. These findings suggest that endothelium-derived NO and PGs may be associated with macrophage lipid accumulation by modulating lipogenesis and cholesterol uptake within these cells.
authors.affiliation: Department of Physiology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: S M
authors.initials: SM
authors.lastname: Senna
authors.forename: R B
authors.initials: RB
authors.lastname: Moraes
authors.forename: M F
authors.initials: MF
authors.lastname: Bravo
authors.forename: R R
authors.initials: RR
authors.lastname: Oliveira
authors.forename: G C
authors.initials: GC
authors.lastname: Miotto
authors.forename: A C
authors.initials: AC
authors.lastname: Vidor
authors.forename: A
authors.initials: A
authors.lastname: Belló-Klein
authors.forename: M C
authors.initials: MC
authors.lastname: Irigoyen
authors.forename: A A
authors.initials: AA
authors.lastname: Belló
authors.forename: R
authors.initials: R
authors.lastname: Curi
authors.forename: P I
authors.initials: PI
authors.lastname: Homem de Bittencourt
mesh_terms: D000085:Acetates / Q000378:metabolism; D000818:Animals; D001158:Arteries / Q000166:cytology; D001161:Arteriosclerosis / Q000503:physiopathology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005227:Fatty Acids / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010743:Phospholipids / Q000096:biosynthesis; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000085:Acetates; D005227:Fatty Acids; D008055:Lipids; D010743:Phospholipids; D011453:Prostaglandins; C110881:S-nitro-N-acetylpenicillamine; D014280:Triglycerides; D009569:Nitric Oxide; D002784:Cholesterol; D013482:Superoxide Dismutase; D010396:Penicillamine; D013755:Tetradecanoylphorbol Acetate