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Formation of 15-hydroxyeicosatetraenoic acid (15-HETE) as the predominant eicosanoid in aortas from Watanabe Heritable Hyperlipidemic and cholesterol-fed rabbits

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      Abstract

      Atherosclerotic plaque formation is accompanied by hyperproliferative events which have many features of an inflammatory response. A high-performance liquid chromatography procedure was developed to analyze the inflammatory prostaglandins, leukotrienes and hydroxyeicosatetraenoic acids (HETEs) produced by aortic segments. Normal rabbit aortas incubated with tritiated arachidonic acid synthesized 12-HETE as the principal lipoxygenase metabolite, and prostacyclin as the major cyclooxygenase product. In contrast, atherosclerotic aortas from both cholesterol-fed and Watanabe Heritable Hyperlipidemic rabbits showed major increases in synthesis of lipoxygenase-derived 15-HETE, which became the predominant eicosanoid in the aortas of both types of rabbit. No leukotrienes or other 5-lipoxygenase products were detected to the detection limit of 0.5 pmol/cm aorta. 15-HETE, which is chemotactic for smooth muscle cells, mitogenic for endothelial cells, and an inhibitor of prostacyclin synthesis may thus play a role in atherogenesis.

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      References

        • Needleman P.
        • Turk J.
        • Jakschik B.A.
        • Morrison A.R.
        • Lefkowith J.B.
        Arachidonic acid metabolism.
        Ann. Rev. Biochem. 1986; 55: 69
        • Simmet T.
        • Peskar B.A.
        Eicosanoids and the coronary circulation.
        Rev. Biochem. Pharm. 1986; 104: 1
        • Willis A.L.
        • Smith D.L.
        • Vigo C.
        Suppression of principal atherosclerotic mechanisms by prostacyclins and other eicosanoids.
        Prog. Lipid Res. 1986; 25: 645
        • Davies P.
        • Bailey P.J.
        • Goldenberg M.M.
        • Ford-Hutchinson A.W.
        The role of arachidonic acid oxygenation in pain and inflammation.
        Ann. Rev. Immunol. 1984; 2: 335
        • Lopes-Virella M.F.
        • Virella G.
        Immunological and microbiological factors in the pathogenesis of atherosclerosis.
        Clin. Immunol. Immunopath. 1985; 37: 377
        • Schwartz C.J.
        • Valente A.J.
        • Sprague E.A.
        • Kelley J.L.
        • Suenram C.A.
        • Graves D.T.
        • Rozek M.M.
        • Edwards E.H.
        • Delgado R.
        Monocyte-macrophage participation in atherogenesis: inflammatory components of pathogenesis.
        Sem. Thromb. Hemostasis. 1986; 12: 79
        • Heam J.A.
        The pathogenesis of atherosclerosis.
        Lancet. 1986; 315: 643
        • Hirosumi J.
        • Nomoto A.
        • Ohkubo Y.
        • Sekiguchi C.
        • Seitaro M.
        • Yamaguchi I.
        • Aoki H.
        Inflammatory responses in cuff-induced atherosclerosis in rabbits.
        Atherosclerosis. 1987; 64: 243
        • Bailey J.M.
        • Butler J.
        Anti-inflammatory drugs in experimental atherosclerosis, Part 1 (Relative potencies for inhibiting plaque formation).
        Atherosclerosis. 1973; 17: 515
        • Mathur S.N.
        • Field F.J.
        • Spector A.A.
        • Armstrong M.L.
        Increased production of lipoxygenase products by cholesterol-rich mouse macrophages.
        Biochim. Biophys. Acta. 1985; 837: 13
        • Mathur S.N.
        • Field F.J.
        Effect of cholesterol enrichment on 12-hydroxyeicosatetraenoic acid metabolism by mouse peritoneal macrophages.
        J. Lipid Res. 1987; 28: 1166
        • Nakao J.
        • Ooyama T.
        • Chang W.
        • Murota S.
        • Orimo H.
        Platelets stimulate aortic smooth muscle cell migration in vitro.
        Atherosclerosis. 1982; 43: 143
        • Nakao J.
        • Ooyama T.
        • Ito H.
        • Chang W.
        • Murota S.
        Comparative effect of lipoxygenase products of arachidonic acid on rat aortic smooth muscle cell migration.
        Atherosclerosis. 1982; 44: 339
        • Shimokawa H.
        • Tomoike H.
        • Nabeyama S.
        • Yamamoto H.
        • Araki H.
        • Nakamura M.
        • Ishii Y.
        • Tanaka K.
        Coronary artery spasm induced in atherosclerotic miniature swine.
        Science. 1983; 221: 560
        • Lee T.H.
        • Austen K.F.
        • Corey E.J.
        • Drazen J.M.
        Leukotriene E4 4-induced airway hyperresponsiveness of guinea pig tracheal smooth muscle cell to histamine and evidence for three separate sulfidopeptide leukotriene receptors.
        in: 7th edn. Proc. Natl. Acad. Sci. USA. 81. 1984: 4922
        • Wittman G.
        • Peskar B.M.
        • Edelmann M.
        • Muller K.M.
        • Simmet T.
        • Peskar B.A.
        Formation of cysteinyl-containing leukotrienes by human arterial tissues.
        Prostaglandins. 1987; 33: 591
        • Forman M.B.
        • Oates J.A.
        • Robertson D.
        • Robertson R.M.
        • Roberts L.J.
        • Virmani R.
        Increased adventitial mast cells in a patient with coronary spasm.
        New Engl. J. Med. 1985; 313: 1138
        • Hartung H.
        • Kladetzky R.G.
        • Melnik B.
        • Hennerici M.
        Stimulation of the scavenger receptor on monocytesmacrophages evokes release of arachidonic acid metabolites and reduced oxygen species.
        Lab. Invest. 1986; 55: 209
        • Schwartz C.J.
        • Sprague E.A.
        • Kelley J.L.
        • Valente A.J.
        • Suenram C.A.
        Aortic intimal monocyte recruitment in the normo- and hypercholesterolemic baboon (Papio cynocephalus).
        Virchow's Arch. 1985; 405: 175
        • Henriksson P.
        • Hamberg M.
        • Diczfalusy U.
        Formation of 15-HETE as a major hydroxyeicosatetraenoic acid in the atherosclerotic vessel wall.
        Biochim. Biophys. Acta. 1985; 834: 272
        • Powell W.S.
        Formation of 6-oxoprostaglandin F, 6,15dioxoprostaglandin f and monohydroxyeicosatetraenoic acids from arachidonic acid by fetal calf aorta and ductus arteriosus.
        J. Biol. Chem. 1982; 257: 9457
        • Setty B.N.Y.
        • Stuart M.J.
        • Walenga R.W.
        Formation of 11-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid in human umbilical arteries is catalyzed by cyclooxygenase.
        Biochim. Biophys. Acta. 1985; 833: 484
        • Bailey J.M.
        • Bryant R.W.
        • Whiting J.
        • Salata K.
        Characterization of 11-HETE and 15-HETE, together with prostacyclin, as major products of the cyclooxygenase pathway in cultured rat aorta smooth muscle cells.
        J. Lipid Res. 1983; 24: 1419
        • Gryglewski R.J.
        • Dembińska-Kièć A.
        • Z̊muda A.
        • Gryglewski T.
        Prostacyclin and thromboxane A2 biosynthesis capacities of heart, arteries, and platelets at various stages of experimental atherosclerosis in rabbits.
        Atherosclerosis. 1978; 31: 385
        • Porter N.A.
        • Logan J.
        • Kontoyiannidou V.
        Preparation and purification of arachidonic acid hydroperoxides of biological importance.
        J. Org. Chem. 1979; 44: 3177
        • Bailey J.M.
        • Butler J.
        Anti-inflammatory drugs in experimental atherosclerosis, Part 5 (Influence of cortisone acetate on short-term and long-term cholesterol fluxes in atherosclerotic aorta).
        Atherosclerosis. 1984; 51: 299
        • Tanzawa K.
        • Shimada Y.
        • Kuroda M.
        • Tsujita Y.
        • Arai M.
        • Watanabe Y.
        WHHL-rabbit: a low density lipoprotein receptor-deficient animal model for familial hypercholesterolemia.
        FEBS Lett. 1980; 118: 81
        • Eskra J.D.
        • Pereira M.J.
        • Ernst M.J.
        Solid phase extraction and high-performance liquid chromatography analysis of lipoxygenase pathway products.
        Anal. Biochem. 1986; 154: 332
      1. 7th edn. Lipid Research Clinics Program, Manual of Laboratory Operations, Vol. I (Lipid and Lipoprotein Analysis) (DHEW Publication, No. (NIH) 75–628). National Institutes of Health, Bethesda, MD1974
        • McGill H.C.
        • Eggen D.A.
        • Strong J.P.
        Atherosclerotic lesions in the aorta and coronary arteries of man.
        in: Roberts J.C. Straus R. Comparative Atherosclerosis. Harper and Row, New York1965: 311
        • Setty B.N.Y.
        • Graeber J.E.
        • Stuart M.J.
        The mitogenic effect of 15- and 12-hydroxyeicosatetraenoic acid on endothelial cells may be mediated via diacylglycerol kinase inhibition.
        J. Biol. Chem. 1987; 262: 17613
        • Moncada S.
        • Gryglewski R.J.
        • Bunting S.
        • Vane J.
        A lipid peroxide inhibits the enzyme in blood vessel microsomes that generates from prostaglandin endoperoxides the substance (prostaglandin X) which prevents platelet aggregation.
        Prostaglandins. 1976; 12: 715
        • Setty B.N.Y.
        • Stuart M.J.
        15-Hydroxy-5,8,11,13-eicosatetraenoic acid inhibits human vascular cyclooxygenase. Potential role in human diabetic vascular disease.
        J. Clin. Invest. 1986; 77: 202
        • Coene M.
        • Bult H.
        • Claeys M.
        • Laekeman G.M.
        • Herman A.G.
        Inhibition of rabbit platelet activation by lipoxygenase products of arachidonic and linoleic acid.
        Thrombosis Res. 1986; 42: 205
        • Thomas G.
        • Ramwell P.
        Induction of vascular relaxation by hydroperoxides.
        Biochem. Biophys. Res. Common. 1986; 139: 102
        • Takahashi M.
        • Ozaki N.
        • Kawakita S.
        • Nozaki M.
        • Saeki Y.
        Vascular effects of 15-hydroperoxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid on canine arteries.
        Jap. J. Pharm. 1985; 37: 325
        • D'Alarao M.
        • Corey E.J.
        • Cunard D.
        • Ramwell P.
        • Uotila P.
        • Vargas R.
        • Wroblewska B.
        The vasodilation induced by hydroperoxy metabolites of arachidonic acid in the rat mesenteric and pulmonary circulation.
        Br. J. Pharmacol. 1987; 91: 627
        • Saito H.
        • Salmon J.A.
        • Moncada S.
        Influence of cholesterol feeding on the production of eicosanoids, tissue plasminogen activator and superoxide anion (O2) by rabbit blood monocytes.
        Atherosclerosis. 1986; 61: 141
        • Turk J.
        • Maas R.L.
        • Brash A.R.
        • Roberts L.J.
        • Oates J.A.
        Arachidonic acid 15-lipoxygenase products from human eosinophils.
        J. Biol. Chem. 1982; 257: 7068
        • Nakao J.
        • Koshihara Y.
        • Ito H.
        • Murota S.
        • Chang W.
        Enhancement of endogenous production of 12l-hy-droxy-5,8,11,13-eicosatetraenoic acid in aortic smooth muscle cells by platelet-derived growth factor.
        Life Sci. 1985; 37: 1435
        • Hopkins N.K.
        • Oglesby T.D.
        • Bundy G.L.
        • Gorman R.R.
        Biosynthesis and metabolism of 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid by human umbilical vein endothelial cells.
        J. Biol. Chem. 1984; 259: 14048