The induced lipoxygenase in atherosclerotic aorta converts linoleic acid to the platelet chemorepellant factor 13-HODE.
Mammalian tissues contain 5-, 12- and 15-lipoxygenases. Only the 15-lipoxygenase can act on linoleic acid, the predominant essential fatty acid of tissues and plasma, producing 13-hydroxyoctadecadienoic acid (13-HODE). Intracellular production of 13-HODE renders endothelial cells resistant to platelet adhesion, while its hydroperoxy precursor, 13-HPODE, synergises with the platelet anti-aggregatory factor prostacyclin. We have found that a 15-lipoxygenase activity is induced in aortas of cholesterol-fed and Watanabe Heritable Hyperlipidemic (WHHL) rabbits. Aortic tissue from WHHL rabbits incubated with 3H-linoleic acid produced a major metabolite identified as 13-HODE, which was formed with an efficiency comparable to the synthesis 15-HETE from arachidonic acid. These findings indicate that the increased aortic 15-lipoxygenase in vascular tissue is capable of producing 13-HODE in vivo. Since platelet adhesion is increased in atherogenesis, and thrombogenesis is a major complication of advanced atherosclerosis, it is suggested that induction of this enzyme may be a protective response to hypercholesterolemia.
Simon
T C
TC
Department of Biochemistry, George Washington University School of Medicine, Washington, DC 20037.
Makheja
A N
AN
Bailey
J M
JM
D000818:Animals; D000991:Antithrombins / Q000378:metabolism; D001011:Aorta / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000502:physiology*; D001091:Arachidonate Lipoxygenases / Q000502:physiology*; D001095:Arachidonic Acids / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D066298:In Vitro Techniques; D008041:Linoleic Acids / Q000096:biosynthesis* / Q000378:metabolism*; D011817:Rabbits
D000991:Antithrombins; D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D008041:Linoleic Acids; D000001:Calcimycin; C024348:13-hydroxy-9,11-octadecadienoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001091:Arachidonate Lipoxygenases; D001093:Arachidonate 15-Lipoxygenase