Formation of 15-hydroxyeicosatetraenoic acid (15-HETE) as the predominant eicosanoid in aortas from Watanabe Heritable Hyperlipidemic and cholesterol-fed rabbits.
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.
Simon
T C
TC
Biochemistry Department, George Washington University School of Medicine, Washington, DC 20037.
Makheja
A N
AN
Bailey
J M
JM
D000818:Animals; D001011:Aorta / Q000032:analysis*; D001161:Arteriosclerosis / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis*; D006949:Hyperlipidemias / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D011817:Rabbits
D006893:Hydroxyeicosatetraenoic Acids; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D002784:Cholesterol; D008084:Lipoxygenase