Deposition of polymerizing fibrin on the vascular endothelium is the final event in intravascular coagulation. Exposure of fibrin clots to confluent monolayers of cultured human endothelial cells for 4 to 24 hours resulted in the disappearance of their normal cobblestone morphology and in the formation of endothelial cell aggregates. The present study was designed to evaluate the conditions and structural requirements of the fibrin clot for the induction of disorganization. Even after harsh treatment with denaturing agents or loading with large amounts of fibrinogen antibodies, polymerized fibrin always induced disorganization of the monolayers. In contrast, soluble fibrin that was kept in solution by either fibrinogen, fragment D-cate, or the tetrapeptide Gly-Pro-Arg-Pro did not cause any alteration of the monolayers. The fibrinogen degradation product D-cate (M r 94,000) itself had no microscopically detectable influence on the monolayer structure. In the absence of fibrin, the effect of thrombin on endothelial cells was found to be distinct from that induced by fibrin; however, the exposure of pieces of glass coverslips caused alterations in morphology indistinguishable from the fibrin-induced disorganization of the monolayer. Experiments using protein-coated polyester films indicated that the ability of the endothelial cells to attach to the overlying material, independent of its chemical structure, is the prerequisite for the induction of disorganization, but not a defined component of the fibrin molecule. Disorganization of vascular endothelium in vivo might be important for the organization and revascularization of an occluding thrombus. (Arteriosclerosis 6:139-145, March/April 1986) T he vascular endothelium contributes anticoagulant as well as procoagulant activities to the regulation of the coagulation system. A nonthrombogenic surface and the expression of fibrinolytic activities by the endothelial cells guarantee the patency of the vascular tree. Surface-bound heparan sulphate, which accelerates the inactivation of thrombin by enhancing the formation of the antithrombin Ill/thrombin complex, 1 and the membrane cofactor thrombomodulin, which facilitates the activation of protein C in conjunction with thrombin, 2 are important surface-mediated mechanisms of the vessel wall that are anticoagulant in nature. In addition, the synthesis and release of prostacyclin 3 and of tissue plasminogen activators 4 account for the inhibition of platelet activation and the continuous lysis of small amounts of fibrin. On the other hand, the synthesis of facator VIIIR:Ag, 56 specific binding of factors IX/IXa and X/Xa, 7 ' 8 and the induction of tissue factor production in the This study was supported by the Stiftung Volkswagenwerk, Hannover, West Germany.Part of this work was presented at the 10th International Congress on Thrombosis and Haemostasis, San Diego, California, in 1985 and is published in abstract form (Thromb Haemostas 1985;54:194).Address for reprints: Dr. Ulrich Delvos, Clinical Research Unit for Blood ...
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