| Institution: | Hemostasis Unit, Hematology Division, Department of Medicine, and the Vascular Pathophysiology Laboratory, Department of Pathology, Brigham and Women's Hospital; and the Departments of Medicine and Pathology, Harvard Medical School, Boston, Massachusetts 02115, U.S.A. |
| Abstract: | Although indirect pharmacologic evidence has suggested the presence of a lipoxygenase pathway of arachidonic acid (AA) metabolism in blood vessels, direct biochemical evidence has been difficult to demonstrate. We have investigated lipoxygenase metabolism in both fresh vessel preparations and cultured vascular cells from various sources and species. Lipoxygenase-derived 3H]HETE (composed of 12-HETE, 15-HETE and 5-HETE), which was abolished by ETYA but not by aspirin, was formed when 3H]AA was incubated with fresh sections of rat aorta. Lipoxygenase activity was lost following deendothelialization. A single peak of 3H]15-HETE was produced by cultured bovine aortic and human umbilical vein endothelial cells (EC) in response to exogenous 3H]AA or from 3H]AA released by ionophore A23187 from endogenous EC membrane phospholipid pools. Cultured bovine, rabbit or rat aorta smooth muscle cells had no detectable 15-lipoxygenase activity. 14C]Linoleic acid was converted by EC to its 15-lipoxygenase metabolite, 14C]13-hydroxyoctadecadienoic acid. These results indicate that blood vessels from different sources and species have a 15-lipoxygenase system, and this activity resides predominantly in the endothelial cells. |
