Potential attenuation of fibrinolysis by growth factors released from platelets and their pharmacologic implications

The American Journal of Cardiology
S FujiiB E Sobel

Abstract

Increased concentrations of the fast-acting tissue-type plasminogen activator (t-PA) inhibitor attenuate the fibrinolytic activity of pharmacologically administered activators of the fibrinolytic system such as t-PA. Accordingly, it was hypothesized that augmentation of synthesis and elaboration of inhibitor from the liver, leading to increased concentrations of inhibitor in plasma, or from endothelial cells in the vicinity of thrombi undergoing lysis, leading to increased concentrations locally, may contribute to failure of pharmacologically induced thrombolysis or to early reocclusion. Because platelets are rich in transforming growth factor beta and epidermal growth factor-like activity, it was thought that release of growth factors from platelets activated in vivo could mediate increases of the inhibitor in plasma by stimulating its formation in the liver and its local release from endothelial cells in the vicinity of thrombi. If so, fibrinolysis might be rendered more effective by concomitant prevention of platelet growth factor release. Transforming growth factor beta, a major constituent of platelets, increased concentrations of the t-PA inhibitor messenger ribonucleic acid (mRNA) in human hepatoma cells in a specific an...Continue Reading

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Citations

Aug 1, 1991·Journal of Cellular Physiology·G E Bergonzelli, E K Kruithof
Jul 11, 1996·European Journal of Pharmacology·R J GryglewskiJ Robak
Oct 1, 1989·Journal of the American College of Cardiology·B E Sobel
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