ENHANCEMENT OF MIGRATION IN BOVINE ENDOTHELIAL-CELLS BY EICOSAPENTAENOIC ACID PRETREATMENT

It has been recognized that endothelial cell migration is an important process in the regeneration of injury in blood vessels. In this study, we examined the effects of polyunsaturated fatty acids on the migration of cultured endothelial cells using a modified Boyden chamber. When endothelial cells isolated from bovine carotid artery were pretreated for 2 days with 5-mu-g/ml of either arachidonic acid, eicosapentaenoic acid or docosahexaenoic acid, every polyunsaturated fatty acid was incorporated substantially into cellular phospholipids. The content of arachidonic acid increased from 9.27 to 23.9% by the arachidonic acid pretreatment, and that of eicosapentaenoic acid and docosahexaenoic acid increased from 9.57 to 11.85% by the eicosapentaenoic acid pretreatment and from 5.56 to 18.40% by the docosahexaenoic acid pretreatment, respectively. Pretreatment of the cells with 0.5-5.0-mu-g/ml of eicosapentaenoic acid resulted in a dose-dependent increase in endothelial migration in response to fetal bovine serum. In contrast, pretreatment of the cells with arachidonic acid and docosahexaenoic acid had no effects on the cell migration. If eicosapentaenoic acid, however, was added directly to the migration assay system instead of the pretreatment, it did not show a profile of chemotactic factor. The eicosapentaenoic acid pretreatment also potentiated cell migration activity in response to several other chemotactic factors such as basic fibroblast growth factor, tumor necrosis factor-alpha and leukotriene C4. The effect of eicosapentaenoic acid on porcine smooth muscle cell migration was also examined. Although eicosapentaenoic acid was similarly incorporated into cellular phospholipids of smooth muscle cells by the pretreatment for 2 days, no stimulative effect was observed in the migration of smooth muscle cells at any doses (0.5-5.0-mu-g/ml). These data suggest that the preventive effect of eicosapentaenoic acid on atherosclerosis is, at least partly, due to its stimulative effect on endothelial cell migration.