Arteriosclerosis, Vol 9, 43-49, Copyright © 1989 by American Heart Association

ARTICLES

Effect of fibrin on endothelial cell production of prostacyclin and tissue plasminogen activator

KL Kaplan, T Mather, L DeMarco and S Solomon
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.

Fibrin formed on endothelial cells has previously been shown to have deleterious effects on the cells. Additionally, substances that cause endothelial cell damage have been reported to induce cultured endothelial cells to synthesize prostacyclin and tissue plasminogen activator (t-PA). The present studies were undertaken to determine whether fibrin formed on cultured human umbilical vein endothelial cells would alter synthesis of prostacyclin and t-PA by the cells. Fibrin was found to increase synthesis of both prostacyclin and t-PA in a dose and time dependent manner. Stimulation of prostacyclin synthesis was completely inhibited by indomethacin; partially inhibited by actinomycin D, cycloheximide, and trifluoperazine; and not affected by cytochalasin D or vinblastine. In contrast, stimulation of t-PA synthesis was completely inhibited by actinomycin D and cycloheximide; partially inhibited by cytochalasin D, vinblastine, and trifluoperazine; and not affected by indomethacin. Fibrin I, formed with Reptilase, caused only slight stimulation of t-PA production, but virtually no stimulation of prostacyclin synthesis. Neither collagen polymerization on the cells nor thrombin added in concentrations that did not induce fibrin polymer formation stimulated production of either substance. Furthermore, soluble fibrin II generated in the presence of the fibrin polymerization inhibitor gly-pro-arg-pro also failed to stimulate either prostacyclin or t-PA production. The presence of platelets in the plasma from which the fibrin was formed did not affect the amount of stimulation of the cells. Fibrin-induced stimulation of endothelial cell production of prostacyclin and t-PA could act to limit vascular occlusion in vivo by inhibiting platelet function and by stimulating fibrinolysis via t-PA.

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