The induced lipoxygenase in atherosclerotic aorta converts linoleic acid to the platelet chemorepellant factor 13-hode

• Published in: Thrombosis research Vol. 55; no. 2; pp. 171 - 178
• Main Authors: Simon, T.C., Makheja, A.N., Bailey, J.M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 15.07.1989
• Subjects: 13-hydroxyoctadecadienoic acid; Animals; Antithrombins - metabolism; Aorta - metabolism; Arachidonate 15-Lipoxygenase - physiology; Arachidonate Lipoxygenases - physiology; Arachidonic Acids - metabolism; Arteriosclerosis - metabolism; atherosclerosis; Calcimycin - pharmacology; Chromatography, High Pressure Liquid; Hydroxyeicosatetraenoic Acids - biosynthesis; In Vitro Techniques; linoleic acid; Linoleic Acids - biosynthesis; Linoleic Acids - metabolism; lipoxygenase; rabbit; Rabbits; atherosclerosis; linoleic acid; lipoxygenase; 13-hydroxyoctadecadienoic acid; rabbit
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/0049-3848(89)90433-7

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.