Platelets stimulate endothelial cells to synthesize type 1 plasminogen activator inhibitor. Evaluation of the role of transforming growth factor beta.
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 micrograms/mL PRthr (1 microgram approximately 10(7) platelets). Neutralizing antibodies to transforming growth factor beta (TGF beta) reduced this effect by 75%. Treatments that activate latent TGF beta (eg, acidification or plasmin) increased this effect approximately fivefold, suggesting that TGF beta in PRthr exists in both a latent (approximately 80%) and an active (approximately 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 TGF beta. These results suggest that platelets can modulate the fibrinolytic system of the endothelium through the release of TGF beta, and that the mechanism by which the platelets are activated can influence the relative amount of active TGF beta.
Slivka
S R
SR
Committee on Vascular Biology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Loskutoff
D J
DJ
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002417:Cattle; D004730:Endothelium, Vascular / Q000378:metabolism*; D005341:Fibrinolysin / Q000494:pharmacology; D005342:Fibrinolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D015849:Plasminogen Inactivators / Q000378:metabolism*; D015539:Platelet Activation; D016212:Transforming Growth Factor beta / Q000502:physiology*
D015849:Plasminogen Inactivators; D016212:Transforming Growth Factor beta; D000244:Adenosine Diphosphate; D005341:Fibrinolysin