Platelets stimulate endothelial cells to synthesize type 1 plasminogen activator inhibitor. Evaluation of the role of transforming growth factor β

Abstract

A model system consisting of thrombin-stimulated bovine platelet releasates (PRthr) and bovine aortic endothelial cells (BAEs) was developed to determine if the interaction between platelets and endothelial cells regulates fibrinolysis. Zymographic analysis indicated that PRthr, treatment of BAEs decreases urokinase and increases type 1 plasminogen activator inhibitor (PAI-1) activity. Although PRthr did not affect the overall rate of BAE protein synthesis, it increased PAI-1 biosynthesis within 6 hours. This increase was complete by 12 hours, with maximum stimulation at 10 to 15 μg/mL PRthr (1 μg ∼ 107 platelets). Neutralizing antibodies to transforming growth factor β (TGFβ) reduced this effect by 75%. Treatments that activate latent TGFβ (eg, acidification or plasmin) increased this effect approximately fivefold, suggesting that TGFβ in PRthr exists in both a latent (∼80%) and an active (∼20%) form. In contrast to PRthr, adenosine diphosphate-prepared platelet releasates did not increase PAI-1 synthesis before acidification, indicating that they contain only the latent form of TGFβ. These results suggest that platelets can modulate the fibrinolytic system of the endothelium through the release of TGFβ, and that the mechanism by which the platelets are activated can influence the relative amount of active TGFβ. © 1991 by The American Society of Hematology.