INVOLVEMENT OF TRANSFORMING GROWTH FACTOR-BETA(1) FOR PLATELETS-INDUCED STIMULATION OF ENDOTHELIN-1 PRODUCTION

1. Possible mechanisms by which platelets stimulate the production of endothelin-1 (ET-1) in vascular endothelial cells (EC) were investigated. 2. A supernatant of platelets stimulated the expression of prepro ET-1 mRNA, followed by an increased secretion of ET-1 from cultured EC. These responses were markedly enhanced by pretreatment of the platelets with thrombin, at a concentration which did not influence the ET-1 production in EC. A platelet suspension, separated from cultured EC by a permeable nylon membrane, also markedly stimulated the ET-1 secretion from EC. 3. Endothelin-1 production enhanced by the platelet supernatant, with or without thrombin pretreatment, correlated with the active transforming growth factor-beta(1) (TGF-beta(1)) concentrations in the supernatant. The supernatant-induced increase in ET-1 secretion from the EC was markedly suppressed by TGF-beta(1) neutralizing antibody. 4. We tentatively conclude that platelets stimulate the endothelial ET-1 production by releasing a bioactive diffusible substance, mainly TGF-beta(1).