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Cellular and Molecular Effects of Thrombin in the Vascular System

  • Chapter
Angiogenesis

Part of the book series: NATO ASI Series ((NSSA,volume 298))

Abstract

Two distinct physiological processes lead to the development of new blood vessels: vasculogenesis and angiogenesis [reviewed by Risau, 1997]. Whereas vasculogenesis is restricted to embryonic development and consists in the differentiation of mesodermal precursor cells into endothelial cells followed by their organisation into the capillary plexus, angiogenesis is the formation of new capillaries from pre-existing blood vessels and takes place both during prenatal and adult life. Angiogenesis can occur under both physiological and pathological conditions such as during wound healing and solid tumour development. Moreover, intra-arterial angiogenesis is evident in atherosclerotic plaques and in recanalised thrombi [reviewed by Eisenstein, 1991]. The cellular and molecular events that lead to angiogenesis are not as yet fully elucidated but are known to include (i) breakdown of the extracellular matrix and of basement membrane of pre-existing blood vessels; (ii) the migration and proliferation of endothelial cells; (iii) production of extracellular matrix allowing the reconstitution of the basement membrane; (iv) recruitment of pericytes and vascular smooth muscle cells (VSMC) to the newly formed blood vessel.

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References

  • Andersson, M., Ostman, A., Westermark, B., Heldin, C-H., 1994. Characterisation of the retention motif in the C-terminal part of the long splice form of platelet-derived growth factor A-chain. J. Biol. Chem. 269: 926–930.

    CAS  PubMed  Google Scholar 

  • Bachhuber, B.G., Sarembock, I.J., Gimble L.W., and Owens, G.K., 1997. Alpha thrombin induces transforming growth factor beta-1 mRNA and protein in cultred vascular smooth muscle cels via a proteolytically activated recetpro. J. Vasc. Res. 34:41–48.

    CAS  PubMed  Google Scholar 

  • Bahou, W.F., Coller, B.S., Potter, C.L., Norton K.J., Kutok J.L., and Goligorsky, M.S., 1993. The thrombin receptor extracellular domain contains sites crucial for peptide ligand-induced activation. J. Clin. Invest. 91: 1405–1413.

    Article  CAS  PubMed  Google Scholar 

  • Bar-Shavit, R., Benezra, D., Eldor, A., Hy-Am, E., Fenton, J.W., II, and Vlodavsky, I., 1990. Thrombin immobilized to extracellular matrix is a potent mitogen for vascular smooth muscle cells: Nonenzymatic mode of action. Cell Regul. 1: 453–463.

    CAS  PubMed  Google Scholar 

  • Bar-Shavit, R., Benezra, M., Sabbah, V., Dejana, E., Vlodavsky, I., and Wilner, G.D., 1992. Functional domains in thrombin outside the catalytic site. In: Berliner, L.J., (ed) “Thrombin: structure and function” Plenum Press: NY and London, pp. 315–350

    Google Scholar 

  • Barger, A., Beeuwkes, R., Lainey, L., Silverman, K., 1984. Hypothesis: vasa vasorum and neovascularization of human coronary arteries. N. Eng. J. Med. 310: 175–177.

    Article  CAS  Google Scholar 

  • Belloni, P.N., Carney, D.H., and Nicolson, G.L., 1992. Organ-derived endothelial cells express differential responsiveness to thrombin and other growth factors. Microvasc. Res. 43:20–45.

    Article  CAS  PubMed  Google Scholar 

  • Benezra, M., Vlodavsky, I., Bar-Shavit, R., 1993. Prothrombin conversion to thrombin by plasminogen activator residing in the subendothelial extracellular matrix. Semin. Thromb. Haemost. 19:405–411.

    Article  CAS  Google Scholar 

  • Benzakour, O., and Kanthou, C., 1996. Cellular and molecular events in atherogenesis: basis for pharmacological and gene therapy approaches to restenosis. Cell Pharmacol. 3:7–22.

    CAS  Google Scholar 

  • Benzakour, O., Kanthou, C., Lupu, F., Dennehy, U., Goodwin, C., Scully, M.F., Kakkar, V.V., and Cooper, D.N., 1955. Prothrombin cleavage by human vascular smooth muscle cells: a potential alternative pathqway to the coagulation cascade. J. Cell Biochem. 59: 514–528.

    Article  Google Scholar 

  • Berk, B.C., Taubman, M.B., Cragoe, E.J., Fenton, J.W., II, and Greindling K.K., 1991. Thrombin-stimulated events in cultured vascular smooth-muscle cells. Biochem. J. 274: 799–805

    CAS  PubMed  Google Scholar 

  • Brass, L.F., 1992. Homologous desensitisation of HEL cell thrombin receptors: distinguishable roles for proteolysis and phosphorylation. J. Biol. Chem. 267: 6044–6050.

    CAS  PubMed  Google Scholar 

  • Brass, L.F., Laposata, F., Banga, H.S., and Rittenhouse, S.E., 1986. Regulation of the phosphoinositide hydrolysis pathway in thrombin-stimulated platelets by a pertussis toxin-sensitive guanine nucleotide-binding protein. J. Biol. Chem. 261: 16833–16847.

    Google Scholar 

  • Brass, L.F., Pizarro, S., Ahuja, M., Belmonte, E., Stadel, J., and Hoxie, J.A., 1994. Changes in the structure and function of the human thrombin receptor during receptor activation, internalisation, and recycling. J. Biol. Chem. 269: 2943–2952.

    CAS  PubMed  Google Scholar 

  • Brass, L.F., Vassallo R.R., Belmonte, E., Ahuja, M., Cichowski, K., and Hoxie, J.A., 1992. Structure and function of the human platelet thrombin receptor. Studies using monoclonal antibodies directed against a defined domain within the receptorN terminus. J. Biol. Chem. 267: 13795–13798.

    CAS  PubMed  Google Scholar 

  • Carney, D.H. 1992. Postclotting cellular effects of thrombin mediated by interactions with high affinity thrombin receptors. In: Berliner, L.J. (ed) “Thrombin: structure and function”. Plenum Press: NY and London, pp. 351–396.

    Google Scholar 

  • Chen, L.B., and Buchanan, J.M., 1975. Mitogenic activity of blood components. Thrombin and Prothrombin. Proc. Natl. Acad. Sci. USA 72: 131–135.

    Article  CAS  PubMed  Google Scholar 

  • Clapham, D.E., and Neer, E.J., 1993. New roles for G-protein bg-dimers in transmembrane signalling. Nature 365: 403–406.

    Article  CAS  PubMed  Google Scholar 

  • Connolly, A., Ishihara, H., Kahn, M., Farese, R.V. Jr., and Coughlin S.R., 1996. Role of thrombin receptor in development and evidence for a second receptor. Nature 381:516–519.

    Article  CAS  PubMed  Google Scholar 

  • Davies, M.J., Bland, M.J., Hangartner, W.R., Angelini, A., and Thomas, A.C., 1989. Factors influencing the presence of acute coronary thrombi in sudden ischaemic death. Eur. Heart. J. 10: 203–208.

    CAS  PubMed  Google Scholar 

  • Eisenstein, R., 1991. Angiogenesis in arteries. Pharmacol Ther. 49: 1–19.

    Article  PubMed  Google Scholar 

  • Esmon, C.T., 1993. Cell-mediated events that control blood coagulation and vascular injury. Annu. Rev. Cell Biol 9: 1–26.

    Article  CAS  PubMed  Google Scholar 

  • Garcia, J.G.N., Aschner, J.L., and Malik, A.B., 1992. Regulation of thrombin-induced endothelial barrier dysfunction and prostaglandin synthesis. In: Berliner, L.J., (ed) “Thrombin: structure and fonction” Plenum Press: NY and London, pp. 397–430.

    Google Scholar 

  • Gerrity, R.G., and Cliff, W.J., 1975. The aortic tunica media of the develooping rat. I. Quantitative stereologic and biochemical analysis. Laborat. Invest. 32: 585–600.

    CAS  PubMed  Google Scholar 

  • Gerszten, R.E., Chen, J., Ishii, M., Ishii, K., Wang, I., Nanevicz, T., Turck, C.W., Vu, T-K.H., and Coughin S.R., 1994. Specificity of the thrombin receptor for agonist peptide is defined by its extracellular surface. Nature 368: 648–651.

    Article  CAS  PubMed  Google Scholar 

  • Haralabopoulos, G.C., Grant, D.S., Kleinman, H.K., Maragoudakis, M.E., 1997. Thrombin promotes endothelial cell alignment in matrigel in vitro and angiogenesis in vivo. Am. J. Physiol. (in press)

    Google Scholar 

  • Hatton, M.W., Moar, S.L., and Richardson, M., 1989. Deendothelialization in vivo initiates a thrombogenic reaction at the rabbit aorta surface. Correlation of uptake of fibrinogen and antithrombin III with thrombin generation by the exposed sub endothelium. Am. J. Pathol. 135: 499–508.

    CAS  PubMed  Google Scholar 

  • Herbert, J-M., Dupuy, E., Laplace, M-C., Zini, J-M., Bar-Shavt, R., and Tobelem G., 1994. Thrombin induces endothelial cell growth via both a proteolytic and a non-proteolytic pathway. Biochem. J. 303: 227–231.

    CAS  PubMed  Google Scholar 

  • Herbert, J-M., Lamarche, I., Prabonnaud, V., Dol, F., and Gauthier, T., 1994. Tissue type plasminogen activator is a potent mitogen for human aortic smooth muscle cells. J. Biol. Chem. 269: 3076–3080.

    CAS  PubMed  Google Scholar 

  • Houck, K.A., Ferrara, N., Winer, I., Cachianes, G., Li, B., and Leung, D.W., 1992. The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol. 5: 1806–1814.

    Article  Google Scholar 

  • Hoxie, J.A., Ahuja, M., Belmonte, E., Pizarro, S., Parton, R., and Brass L.F., 1993. Internalisation and recycling of activated thrombin receptors. J. Biol. Chem. 268: 13756–13763.

    CAS  PubMed  Google Scholar 

  • Huang, C.L., and Ives, H.E., 1987. Growth inhibition by protein kinase C late in mitogenesis. Nature 329: 849–850.

    Article  CAS  PubMed  Google Scholar 

  • Hung, D.T., Wong, Y.H., Vu, T-K.H., and Coughlin, S.R., 1992. The cloned platelet thrombin receptor couples to at least two distinct effectors to stimulate phosphoinositide hydrolysis and inhibit adenylyl cyclase. J. Biol Chem. 267: 20831–20834.

    CAS  PubMed  Google Scholar 

  • Ishihara, H., Connolly, A.J., Zeng, D., Kahn, M.L., Zheng Y.W., Timmons, C., Tram, T., and Coughlin S.R., 1997. Protease-activated receptor 3 is a second thrombin receptor in humans. Nature 386: 502–506.

    Article  CAS  PubMed  Google Scholar 

  • Ishii, K., Chen J., Ishii, M., Koch, W.J., Freedman, N.J., Lefkowitz, R.J., and Coughlin S.R., 1994. Inhibition of thrombin receptor signalling by a G-protein coupled receptor kinase: functional specificity among G-protein coupled receptor kinases. J. Biol. Chem. 269: 1125–1130.

    CAS  PubMed  Google Scholar 

  • Ishii, K., Hein, L., Kobilka, B., and Coughlin, S.R., 1993. Kinetics of thrombin receptor cleavage on intact cells. Relation to signaling. J. Biol. Chem. 268: 9780–9786.

    CAS  PubMed  Google Scholar 

  • Kaetzel, D.M., Coyne, D.W., and Fenstermaker, R.A., 1993. Transcriptional control of the platelet derived growth factor subunit genes. Biofactors 4: 71–81.

    CAS  PubMed  Google Scholar 

  • Kahan, C., Seuwen, K., Meloche, S., and Pouyssegur, J., 1992. Coordinate, biphasic activation of p44 mitogen-activated protein kinase and S6 kinase by growth factors in hamster fibroblasts. J. Biol. Chem. 267: 13369–13375.

    CAS  PubMed  Google Scholar 

  • Kanse, S.M., Benzakour, O., Kanthou, C., Kost, C., Lijnen, R., and Preissner, K.T., 1997. Urokinase-type plasminogen activator stimulates hyman vascular smooth muscle cell proliferation. Atheroscl. Thromb. Vasc. Biol., (in press).

    Google Scholar 

  • Kanthou, C., and Benzakour, O., 1995. Cellular effects of thrombin and their signalling pathways. Cell Pharmacol. 2: 293–302.

    CAS  Google Scholar 

  • Kanthou, C., Benzakour, O., Patel, G., Deadman, J., Kakkar, V.V., and Lupu, F., 1995a. Thrombin receptor activating peptide (TRAP) stimulates mitogenesis, c-fos and PDGF-A gene expression in human vascular smooth muscle cells. Thromb. Haemost. 74: 1340–1347.

    CAS  PubMed  Google Scholar 

  • Kanthou, C., Kanse, S.M., Kakkar, V.V., and Benzakour, O., 1996. Involvement of pertussis toxin sensitive and insensitive G proteins in thormbin signalling on cultured human vacular smooth muscle cells. Cell. Signall. 8: 59–66.

    Article  CAS  Google Scholar 

  • Kanthou, C., Kanse, S.M., Newman, P., Kakkar, V.V., and Benzakour, O., 1995b. Structural domains of thormbin involved in the induction of mitogenesis in cultured human vascular smooth muscle cells. Blood Coag. Fibr. 6: 634–642.

    Article  CAS  Google Scholar 

  • Kanthou, C., Parry, G., Wijelath, E., Kakkar, V.V., and Demoliou-Mason, C., 1992. Thrombin-induced proliferation and expression of platelet-derived growth factor-A chain gene in human vascular smooth muscle cells. FEBS Lett. 314: 134–148.

    Article  Google Scholar 

  • Ku, P.T., and D’Amore, P.A., 1995. Regulation of basic fibroblast growth factor (bFGF) gene and protein expression following its release from sublethally injured endothelial cells. J. Cell Biochem. 58: 328–343.

    Article  CAS  PubMed  Google Scholar 

  • Li, X.N., Varma, V.K., Parks, J.M., Benza, R.L., Koons J.C., Grammer, JR., Grenett, H., Tabengwa, E.M., and Booyse F.M., 1995. Thombin decreases the urokinase receptor and surface localized fibrinolysis in cultured endothelial cells. Arteroscler. Thromb. 15: 410–419.

    Article  CAS  Google Scholar 

  • Lin, L-L., Wartmann, M., Lin, A.Y., Knopf, J.L, Scih, A.A., and Davis R.J., 1993. cPLA2 is phosphorylated and activated by MAP kinase. Cell 72: 269–278.

    Article  CAS  PubMed  Google Scholar 

  • Lombardi, D.M.M., Reidy, M.A., and Schwartz, S.M., 1991. Methodologic considerations important in the accurate quntitation of aortic smooth muscle cell replication in the normal rat. Am. J. Pathol. 138: 441–446.

    CAS  PubMed  Google Scholar 

  • Magnaldo, I., Pouyssegur, J., and Paris, S., 1988. Thrombin exerts a dual effect on stimulated adenylate cyclase in hamster fibroblasts: an inhibition via a GTP-binding protein and a potentiation via activation of protein kinase C. Biochem. J. 253: 711–719.

    CAS  PubMed  Google Scholar 

  • Majesky, M.W., Reidy, M.A., Bowen-Pope, D.F., Hart, C.E., Wilcox, J.N., and Schwartz, S.M., 1990. PDGF ligand and receptor gene expression during repair or arterial injury. J. Cell Biol. 111:2149–2158.

    Article  CAS  PubMed  Google Scholar 

  • Mann, K.G., 1994. Prothrombin and Thrombin. In Colman, R.W., Hirsh, J., Marder, V.J., and Salzman, E.W., (eds): “Haemostasis and Thrombosis: Basic Principles and Clinical Practice”. Lippincott Company: Philadelphia, pp. 184–199.

    Google Scholar 

  • Maragoudakis, M., E., 1996. The role of thormbinin angiogenesis. In: “Molecular, Celluar and Clinical Aspects of Angiogenesis”‘Ed. Maragoudakis, Plenum Press, pp 115–124.

    Chapter  Google Scholar 

  • McNamara, C.A., Sarembock, I.J., Gimple, L.W., Fenton, J.W., II, Coughlin, S.R., and Owens, G.K., 1993. Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor. J. Clin. Invest. 91: 94–98.

    Article  CAS  PubMed  Google Scholar 

  • Molloy, C.J., Pawlowski, J.E., Taylor, D.S., Turner, C.E., Weber, H., Peluso, M., and Seiler, S.M., 1996. Thrombin receptor activation elicits rapid protein tyrosine phosphorylatin and stimulation of the raf-1/MAP kinase pathway preceding delayed mitogenesis in cultured rat aortic smooth muscle cells. J. Clin. Invest. 97: 1173–1183.

    Article  CAS  PubMed  Google Scholar 

  • Ngaiza, J.R., and Jaffe, E.A., 1991. A 14 amino acid peptide derived from the amino terminus of the cleaved thrombin receptor elevates intracellular calcium and stimulates prostacycline production by human endothelial cells. Biochem. Biophys. Res. Commun. 179: 1656–1661.

    Article  CAS  PubMed  Google Scholar 

  • Noda-Heiny, H., Fujii, S., and Sobel, B.E., 1993. Induction of vascular smooth muscle cell expression of plasminogen activator inhibitor-1 by thrombin. Circ. Res. 72: 36–43.

    Article  CAS  PubMed  Google Scholar 

  • Obberghen-Schilling, E.V., and Pouyssegur, J., 1993. a-Thrombin receptors and growth signalling. Semin. Thromb. Haem. 19: 378–385.

    Article  Google Scholar 

  • Okada, S.S., Grobmyer, S.R., and Barnathan E.S., 1996. Contrasting effects of plasminogen activators, urokinase receptor and LDL receptor-related protein on smooth muscle cell migration and invation. Arterioscler. Thromb. Vasc. Biol. 16: 1269–1276.

    Article  CAS  PubMed  Google Scholar 

  • Okazaki, H., Majesky, M.W., Harker, L.A., and Schwartz, S.M., 1992. Regulation of platelet-derived growth factor ligand and receptor gene expression by a-thrombin in vascular smooth muscle cells. Circ. Res. 71: 1285–1293.

    Article  CAS  PubMed  Google Scholar 

  • Pearson, J.D., 1994. Endothelial cell function and thrombosis. Baillieres Clinical Haematology 7: 441–452.

    Article  CAS  Google Scholar 

  • Pepper, M.S., Montesano, R., Mandriota, S., Orci, L., and Vassalli, J-D., 1996. Angiogenesis: a paradigm for balanced extracellular proteolysis during cell migratio and morphogenesis. Enzyme Protein 49: 138–162.

    CAS  PubMed  Google Scholar 

  • Rade, J.J., Schulick, A.H., Virmani, R., and Dichek, D.A., 1996. Local adenoviral-mediated expression of recombinant hirudin reduces neointima formation after arterial injury. Nature Med. 2: 293–298.

    Article  CAS  PubMed  Google Scholar 

  • Raines, E.W., and Ross, R., 1992. Compartmentalisation of PDGF on extracellular binding sites dependent on exon 6 encoded sequences. J. Cell Biol. 116: 553–543.

    Article  Google Scholar 

  • Rasmussen, U.B., Vouret-Craviari, V., Jallat, S., Schlesinger, Y., Pages, G., Pavirani, A., Lecocq, J-P., Pouyssegur, J., and Van Obberghen-Schilling, E., 1991. cDNA cloning and expression of a hamster a-thrombin receptor coupled to Ca2+ mobilization. FEBS Lett 288: 123–128.

    Article  CAS  PubMed  Google Scholar 

  • Reuning, U., Little S.P., Dixon, E.P., and Bang, N.U. 1994. Effect of thormbi, the thrombin receptor activation peptide, and other mitogens on vascular smooth muscle cell urokinase receptor mRNA levels. Blood 84: 3700–3708.

    CAS  PubMed  Google Scholar 

  • Risau, W., 1997. Mechanisms of angiogenesis. Nature 386: 671–674.

    Article  CAS  PubMed  Google Scholar 

  • Ross, R., 1993. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362: 801–809.

    Article  CAS  PubMed  Google Scholar 

  • Scarpati, E.M., and DiCorleto, P.E., 1996. Identification of a thrombin response element in the human platelet-derived growth factor B-chain (c-sis) promoter. J. Biol. Chem. 271: 3025–3032.

    Article  CAS  PubMed  Google Scholar 

  • Schaeffer, P., Riera, E., Dupuy, E., and Herbert J.M., 1997. Non-proteolytic activation of thro thrombin receptor promotes human umbilical vein endothelial cell growth but not intracellular Ca2+ prostacyclin or permeablility. Biochem. Pharmacol. 53: 487–491.

    Article  CAS  PubMed  Google Scholar 

  • Sekiya, F., Usui, H., Inoue, K., Fukudome K., Morita, T., 1994. Activation of prothrombin by a novel membrane-associated protease. J. Biol. Chem. 269: 32441–32445.

    CAS  PubMed  Google Scholar 

  • Scihi, N., and Brookes, M., 1971. Ultrastructure of the blood vessels in the chick allantois and chorioallantois. J. Anat. 109: 1–5.

    Google Scholar 

  • Shankar, R, de la Motte, C.A., Poptic, E.J., and Dicorletto, P.E., 1994. Thrombin receptor-activating peptides differentially stimulate platelet-derived growth factor production, monocytic cell adhesion, and E-selectin expression in human umbilical vein endothelial cells. J. Biol. Chem. 269: 13936–13941.

    CAS  PubMed  Google Scholar 

  • Sternberg, J., Redin, W.R., Warner, W.S., and Carney, D.H., 1993. The Role of thrombin and the thrombin receptor activating peptide (TRAP-508) in initiation of tissue repair. Thromb. Haemost. 70: 158–162.

    Google Scholar 

  • Taipale, J., Koli, K., and Keski-Oja, J., 1992. Release of transforming growth factor-b1 from the pericellular matrix of cultured fibroblasts and fibrosarcoma cells by plasmin and thrombin. J. Biol. Chem. 267: 25378.

    CAS  PubMed  Google Scholar 

  • Taparelli, C., Metternich, R., Ehrhardt, C., and Cook, N.S., 1993. Synthetic low-molecular weight thrombin inhibitors: molecular design and pharmacological profile. TIPS 14: 366–376.

    Google Scholar 

  • Trejo, J.A., Connolly, A.J., and Coughlin, S.R., 1996. The cloned thrombin receptor is necessary and sufficient for activtion of mitogen-activated protein kinase and mitogenesis in mouse lung fibroblasts. J. Biol. Chem. 271: 21536–21541.

    Article  CAS  PubMed  Google Scholar 

  • Tsopanoglou, N.E., Pipili-Synetos, E., and Maragoudakis, M.E., 1993. Thrombin promotes angiogenesis by a mechanism independent of fibrin formation. Am. J. Physiol. 264: C1302–1307.

    Google Scholar 

  • Vlodavsky, I., Folkman, J., Sullivan, R., Fridman, R., Ishai-Michaeli, R., Sasse, J., and Klagsbrun M., 1987. Endothelial cell-derived basic fibroblast growth factor: Synthesis and deposition into subendothelial extracellular matrix. Proc. Natl. Acad. Sci. USA 84: 2292–2296.

    Article  CAS  PubMed  Google Scholar 

  • Vouret-Craviari, V., Grall, D., Chambard, J-C., Rasmussen U.B., Pouyssegur, J., and Van Obberghen-Schilling, E., 1995. Post translational and activation-dependent modifications of the G-protein coupled thrombin receptor. J. Biol. Chem. 270: 8367–8372.

    Article  CAS  PubMed  Google Scholar 

  • Vouret-Craviari, V., Van Obberghen-Schilling, E., Scimeca J-C., Van Obberghen, E., and Pouyssegur J., 1993. Differential activation of p44mapk (ERK1) by a-thrombin and synthetic receptor peptide agonists. Biochem. J. 289: 209–214.

    CAS  PubMed  Google Scholar 

  • Vouret-Craviari, V., Van Obberghen-Schilling, E., Rasmusse, U.B., Paviran, A., Lecocq, J-P., and Pouyssegur, J., 1992. Synthetic a-thrombin receptor peptides activate G-protein coupled signalling pathways but are unable to induce mitogenesis. Mol. Biol. Cell 3: 95–102.

    CAS  PubMed  Google Scholar 

  • Vu, T-K.H., Hung, D.T., Wheaton, V.I., and Coughlin, S.R., 1991. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 64: 1057–1068.

    Article  CAS  PubMed  Google Scholar 

  • Walters, T.K., Gorog, D.A., and Wood, R.F.M., 1994. Thrombin generation following arterial injury is a critical initiating event in the pathogenesis of the proliferative stages of the atherosclerotic process. J. Vase. Res. 31: 173–177.

    Article  CAS  Google Scholar 

  • Wang, H.S., Li, F., Runge, M.S., and Chaikof, E.L., 1997. Endothelial cells exhibit differential chemokinetic and mitogenic responsiveness to alpha thormbin. J. Surg. Res. 68: 139–144.

    Article  CAS  PubMed  Google Scholar 

  • Weiss, R.H., and Maduri, M., 1993. The mitogenic effect of thrombin in vascular smooth muscle cells is largely due to basic fibroblast growth factor. J. Biol. Chem. 268: 5724–5727.

    CAS  PubMed  Google Scholar 

  • Weitz, J.I., Hudoba, M., Massel, D., Maraganore, J.M., and Hirsh, J., 1990. Clotbound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin Ill-independent inhibitors. J. Clin. Invest. 86: 385–391.

    Article  CAS  PubMed  Google Scholar 

  • Wilcox, J.N., Rodriguez, J., Subramanian, R., Ollerenshaw, J., Zhong, C., Hayzer, D.J., Horaist, C., Hanson, S.R., Lumsden A., Salam, T.A., Kelly, A.B., Harker, LA., and Runge, M., 1994. Characterisation of thrombin receptor expression during vascular lesion formation. Circ. Res. 75: 1029–1039.

    Article  CAS  PubMed  Google Scholar 

  • Wojta, J., Gallicchio, M., Zoellner, H., Hufnagl, P., Last, K., Filonzi, E.L., Binder, B.R., Hamilton, J.A., and McGrath, K., 1993. Thrombin stimulates expression of tissue-type plasminogen activator and plasminogen activator inhibitor type 1 in cultured human vascular smooth muscle Cells. Thromb. Haemost. 70: 469–474.

    CAS  PubMed  Google Scholar 

  • Woolkalis, M.J., and Brass, L.F., 1994. Thrombin receptor cleavage and intemalisation in human umbilical endothelial cells. FASEB J.. 8: A 1385.

    Google Scholar 

  • Zoldhelyi, P., Bichler, J., Owen, W.G., Grill, D.E., Fuster, V., Mruk, J.S., Chesebro, J.H., 1994. Persistent thrombin generation in humans during specific thrombin inhibition with hirudin. Circulation 90: 2671–2678.

    Article  CAS  PubMed  Google Scholar 

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  1. Thrombosis Research Institute, Emmanuel Kaye Building, Manresa Road, London, SW3 6LR, UK

    Chryso Kanthou, Vijay Vir Kakkar & Omar Benzakour

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  1. Chryso Kanthou
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  2. Vijay Vir Kakkar
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  1. University of Patras Medical School, Patras, Greece

    Michael E. Maragoudakis

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Kanthou, C., Kakkar, V.V., Benzakour, O. (1998). Cellular and Molecular Effects of Thrombin in the Vascular System. In: Maragoudakis, M.E. (eds) Angiogenesis. NATO ASI Series, vol 298. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9185-3_27

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