Serotonin-induced endothelial cell proliferation is blocked by omega-3 fatty acids

Serotonin (5HT) released from aggregating platelets at sites of vascular in jury is a known mitogen for vascular endothelial cells, Recent studies have indicated that regenerating endothelial cells at sites of vessel wall inju ry may play a role in the development of restenosis by synthesizing and rel easing growth factors for vascular smooth muscle cells, proliferation of wh ich may result in the development of neointima, Diets rich in fish oils (om ega-3 fatty acids) are associated with reduced risk of cardiovascular disea se including atherosclerosis and restenosis. This study examined the effect of the omega-3 and other fatty acids, eicosapentaenoic acid (EPA) and doco sahexaenoic acid (DHA), on 5HT induced endothelial cell proliferation. Amon g the fatty acids examined only EPA and DHA could reverse the mitogenic eff ect of 5HT on vascular endothelial cells, whereas oleic acid or palmitic ac id did not have any effect. When added together, EPA and DHA potentiate eac h other in reversing the mitogenic effect of 5HT. EPA and DHA also inhibite d the 5HT-induced increase in the 5HT(2) receptor mRNA, without a change in the receptor density or affinity. This data suggests that one of the mecha nisms by which omega-3 fatty acids may attenuate the development of atheros clerosis or restenosis is to inhibit the mitogen induced growth of vascular endothelial cells, which attenuates the release of growth factors for vasc ular smooth muscle cells.