Abstract
Tissue factor is a transmembrane protein that activates the extrinsic coagulation pathway by binding factor VII. Endothelial cells, being in contact with circulating blood, do not normally express tissue factor. Here we provide evidence that oxygen free radicals induce tissue factor messenger RNA transcription and expression of tissue factor procoagulant activity in endothelial cells in culture. Isolated, perfused rabbit hearts exposed to exogenous oxygen free radicals also showed a marked increase in tissue factor activity within the coronary circulation. Furthermore, in ex vivo and in vivo hearts subjected to ischemia and reperfusion, a condition associated with a production of oxygen free radicals in large amounts, a marked increase in tissue factor activity occurred. This phenomenon could be abolished by oxygen radical scavengers. This increase in tissue factor activity during postischemic reperfusion was accompanied by a significant decrease in coronary flow, suggesting that increase in tissue factor activity with the consequent activation of the coagulation cascade might impair coronary flow during reperfusion and possibly contribute to the occurrence of reperfusion injury.
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References
Nemerson, Y. Tissue factor and hemostasis. Blood 71, 1–8 (1988).
Colucci, M. et al. Cultured human endothelial cells generate tissue factor in response to endotoxin. J. din. Invest. 71, 1893–1991 (1983).
Nawroth, P.P., Handley, D.A., Esmon, C.T. & Stern, D.M. Interleukin-1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity. Proc. Natl. Acad. Sci.USA 83, 3460–3465 (1986).
Zweier, J.L., Flaherty, J.T. & Weisfeldt, M.L. Direct measurements of free radical generation following reperfusion of ischemic myocardium. Proc. Natl. Acad. Sci. USA 84, 1404–1407 (1987).
Zweier, J.L. et al. Measurement and characterization of post-ischemic free radical generation in the isolated perfused heart. J. Biol. Chem. 264, 18890–18895 (1989).
Ambrosio, G. et al. Oxygen radicals generated at reflow induce peroxidation of membrane lipids in reperfused hearts. J. Clin. Invest. 87, 2056–2066 (1991).
Halliwell, B. Oxidants and human disease: Some new concepts. FASEB J. 1, 358–364 (1987).
McCord, J.M. Oxygen-derived free radicals in post-ischemic tissue injury. N. Engl. J. Med. 312, 159–163 (1985).
Sies, H. & Cadenas, E. Oxidative stress: Damage to intact cells and organs. Philos. Trans. R. Soc. Land. B. Biol. Sci. 311, 617–631 (1985).
Ambrosio, G. et al. Modulation of platelet function by reactive oxygen metabolites. Am. J. Physiol. 267, H308–H318 (1994).
Ambrosio, G. et al. Oxygen radicals inhibit human plasma acetylhydrolase, the enzyme that catabolizes platelet-activating factor. J. Clin. Invest. 93, 2408–2416 (1994).
Yao, S.K. et al. Active oxygen species play a role in mediating platelet aggregation and cyclic flow variations in severely stenosed and endothelium-injured coronary arteries. Circ. Res. 73, 952–967 (1993).
Zweier, J.L., Kuppusamy, P. & Lutty, G.A. Measurements of endothelial cell free radical generation: Evidence for a central mechanism of free radical injury in postischemic tissues. Proc. Natl. Acad. Sci. USA 85, 4046–4050 (1988).
Zweier, J.L., Broderick, R., Kuppusamy, P., Thompson-Gorman, S. & Lutty, G.A. Determination of the mechanism of free radical generation in human aortic endothelial cells exposed to anoxia and reoxygenation. J. Biol. Chem. 269, 24156–24162 (1994).
Pawashe, A.B. et al. A monoclonal antibody against rabbit tissue factor inhibits thrombus formation in stenotic injured rabbit carotid arteries. Circ. Res. 74, 56–63 (1994).
Ambrosio, G., Jacobus, W.E., Bergman, C.A., Weisman, H.F. & Becker, L.C. Preserved high energy phosphate metabolic reserve in globally “stunned” hearts despite reduction of basal ATP content and contractility. J. Mol. Cell. Cardiol. 19, 953–964 (1987).
Connelly, C., Vogel, W.M., Hernandez, Y.M. & Apstein, C.S. Movement of necrotic wavefront after coronary artery occlusion in rabbit. Am. J. Physiol. 243, H682–H690 (1982).
Esmon, C.T. & Owen, W.G. Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. Proc. Natl. Acad. Sci. USA 78, 2249–2255 (1981).
Bajaj, M.S., Kuppuswamy, M.N., Saito, H., Spitzer, S.G. & Bajaj, S.P. Cultured normal human hepatocytes do not synthesize lipoprotein-associated coagulation inhibitor: Evidence that endothelium is the principal site of its synthesis. Proc. Natl. Acad. Sci. USA 87, 8869–8872 (1990).
Moncada, S., Gryglewski, R., Bunting, S. & Vane, J.R. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263, 663–665 (1976).
Golino, P. et al. Endothelium-derived relaxing factor modulates platelet aggregation in an in vivo model of recurrent platelet activation. Circ. Res. 71, 1447–1453 (1992).
Jaffe, E.A. Endothlial cell structure and function. in Hematology: Basic Principles and Practice (eds Hoffman, R., Benj, E.J., Shattil, S.J., Furie, B. & Cohen, H.J.) 1198–1210 (New York, Churchill Livingstone, New York, 1991).
Grossman, D.C., Carr, D.P., Tuddenham, E.G.D., Pearson, J.D., & McVey, J.H. The regulation of tissue factor mRNA in human endothelial cells in response to endotoxin or phorbol ester. J. Biol. Chem. 265, 9782–9787 (1990).
Clauss, M. et al. A polypeptide factor produced by fibrosarcoma cells that induces endothelial tissue factor and enhances the procoagulant response to tumor necrosis factor/cachectin. J. Biol. Chem. 265, 7078–7083 (1990).
Kao, J. et al. Endothelial monocyte-activating polypeptide II: A novel tumor-derived polypeptide that activates host-response mechanisms. J. Biol. Chem. 267, 20239–20247 (1992).
Hartzell, S., Ryder, K., Lanahan, A., Kau, L.F. & Nathans, D. A growth-factor responsive gene of murine BALB/c 3T3 cells encodes a protein homologous to human tissue factor. Mol. Cell. Biol 9, 2567–2573 (1989).
Bloem, L.J., Chen, L., Konigsberg, W.H. & Bach, R. Serum stimulation of quiescent human fibroblast induces the synthesis of tissue factor mRNA followed by the appearance of tissue factor antigen and procoagulant activity. J. Cell. Physiol. 139, 418–423 (1989).
Marmur, J.D. et al. Tissue factor is rapidly induced in arterial smooth muscle after balloon injury. J. Clin. Invest. 91, 2253–2259 (1993).
Ambrosio, G., Weisman, H.F., Mannisi, J.A. & Becker, L.C. Progressive impairment of regional myocardial perfusion after initial restoration of post-ischemic blood flow. Circulation 80, 1846–1861 (1989).
Yuzawa, Y. et al. Antibody-mediated redistribution and shedding of endothelial antigens in the rabbit. J. Immunol. 150, 5633–5646 (1993).
Chomczynski, P., & Sacchi, N. Single-step method of RNA isolation by acid guanidinium thiocynate-phenol-chloroform extraction. Anal. Biochem. 162, 156–159 (1987).
Pawashe, A. et al. Molecular cloning, characterization, and expression of cDNA for rabbit brain tissue factor. Thromb. Haemost. 66, 315–320 (1991).
Ogawa, S. et al. Hypoxia modulates the barrier and coagulant function of cultured bovine endothelium. J. Clin. Invest. 85, 1090–1098 (1990).
Golino, P. et al. Endogenous prostaglandin endoperoxides may alter infarct size in the presence of thromboxane synthase inhibition: Studies in a rabbit model of coronary artery occlusion-reperfusion. J. Am. Coll. Cardiol. 21, 493–501 (1993).
Kowailik, P. et al. Measurement of regional myocardial blood flow with multiple colored microspheres. Circulation 83, 974–982 (1991).
Schosser, R., Arfors, K.-E. & Messmer, K. MIC-II — A program for the determination of cardiac output, arterio-venous shunt and regional blood flow using the radioactive microsphere method. Comput. Programs Biomed, 9, 19–38 (1979).
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Golino, P., Ragni, M., Cirillo, P. et al. Effects of tissue factor induced by oxygen free radicals on coronary flow during reperfusion. Nat Med 2, 35–40 (1996). https://doi.org/10.1038/nm0196-35
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DOI: https://doi.org/10.1038/nm0196-35
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