Download PDF
Thromb Haemost 1998; 80(03): 506-511
DOI: 10.1055/s-0037-1615237
Rapid Communications
Schattauer GmbH

Fibrin-Rich and Platelet-Rich Thrombus Formation on Neointima: Recombinant Tissue Factor Pathway Inhibitor Prevents Fibrin Formation and Neointimal Development following Repeated Balloon Injury of Rabbit Aorta

Yujiro Asada
1   From the First Department of Pathology, Miyazaki Medical College, Miyazaki, Japan and The Chemo-Sero-Therapeutic Research Institute, Kumamoto, Japan
,
Seiichiro Hara
1   From the First Department of Pathology, Miyazaki Medical College, Miyazaki, Japan and The Chemo-Sero-Therapeutic Research Institute, Kumamoto, Japan
,
Atsushi Tsuneyoshi
1   From the First Department of Pathology, Miyazaki Medical College, Miyazaki, Japan and The Chemo-Sero-Therapeutic Research Institute, Kumamoto, Japan
,
Kinta Hatakeyama
1   From the First Department of Pathology, Miyazaki Medical College, Miyazaki, Japan and The Chemo-Sero-Therapeutic Research Institute, Kumamoto, Japan
,
Atsushi Kisanuki
1   From the First Department of Pathology, Miyazaki Medical College, Miyazaki, Japan and The Chemo-Sero-Therapeutic Research Institute, Kumamoto, Japan
,
Kousuke Marutsuka
1   From the First Department of Pathology, Miyazaki Medical College, Miyazaki, Japan and The Chemo-Sero-Therapeutic Research Institute, Kumamoto, Japan
,
Yuichiro Sato
1   From the First Department of Pathology, Miyazaki Medical College, Miyazaki, Japan and The Chemo-Sero-Therapeutic Research Institute, Kumamoto, Japan
,
Yu-ichi Kamikubo
1   From the First Department of Pathology, Miyazaki Medical College, Miyazaki, Japan and The Chemo-Sero-Therapeutic Research Institute, Kumamoto, Japan
,
Akinobu Sumiyoshi
1   From the First Department of Pathology, Miyazaki Medical College, Miyazaki, Japan and The Chemo-Sero-Therapeutic Research Institute, Kumamoto, Japan
› Author Affiliations
Further Information

Publication History

Received 21 November 1997

Accepted after resubmission 07 May 1998

Publication Date:
08 December 2017 (online)

    Permissions and Reprints

Summary

Thrombus formation and neointimal growth are the critical events in restenosis after balloon angioplasty. However, the responses of diseased vessels to injuries caused by balloon angioplasty have not been well examined. We investigated the thrombus formation and neointimal development following the balloon injury to the previously induced neointima in the rabbit aorta and the effects of recombinant tissue factor pathway inhibitor (rTFPI) on these responses. Rabbit thoracic aortas were subjected to injury with a Fogarty 4F balloon catheter at 1.75 atm (first injury), and 4 weeks later the same vessels were subjected to the second injury with a Swan-Ganz 5F balloon catheter at 1.4 atm (mild-injury group) or 1.8 atm (severe-injury group), and immediately after that a retrograde bolus injection of rTFPI (100 μg/kg body weight) or saline was performed into the injured segments via the central tube of the Swan-Ganz catheter. Twenty minutes after the second injury, the injured surfaces were covered with platelet-rich thrombi in the mild-injury group and with fibrin-rich thrombi in the severe-injury group. Damaged intimal smooth muscle cells, which were immunohistochemically positive for tissue factor (TF), were observed beneath the fibrin-rich thrombi. The neointima 4 weeks after the second injury was significantly thicker in the severe-injury group than in the mild-injury group. The bolus infusion of rTFPI markedly inhibited fibrin formation on the injured surfaces, and significantly reduced the neointimal development in the severe-injury group at 4 weeks after the second injury. These results indicate that TF-dependent coagulation pathway is primarily responsible for fibrin-rich thrombus formation and may play an important role in neointimal development following the balloon injury to the rabbit aortic neointima. Additionally the bolus administration of rTFPI to the injured vessels could prevent mural thrombus formation and neointimal growth after balloon angioplasty.

 

  • References

  • 1 Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362: 801-9.
    CrossrefPubMedGoogle Scholar
  • 2 Ferns GAA, Stewart-Lee AL, Änggård EE. Arterial response to mechanical injury: balloon catheter de-endothelialization. Atherosclerosis 1992; 92: 89-104.
    CrossrefPubMedGoogle Scholar
  • 3 Ip JH, Fuster V, Israel D, Badimon L, Badimon J, Chesebro JH. The role of platelets, thrombin, and hyperplasia in restenosis after coronary angioplasty. J Am Coll Cardiol 1991; 17 Suppl B 77B-88B.
    PubMedGoogle Scholar
  • 4 Majesky MW, Reidy MA, Bowen-Pope DF, Hart CE, Wilcox JN, Schwartz SM. PDGF ligand and receptor gene expression during repair of arterial injury. J Cell Biol 1990; 111: 2149-58.
    CrossrefPubMedGoogle Scholar
  • 5 Olson NE, Chao S, Lindner V, Reidy MA. Intimal smooth muscle cell proliferation after balloon catheter injury: the role of basic fibroblast growth factor. Am J Pathol 1992; 140: 1017-23.
    PubMedGoogle Scholar
  • 6 Koyama H, Reidy MA. Reinjury of arterial lesions induces intimal smooth muscle cell replication that is not controlled by fibroblast growth factor 2. Circ Res 1997; 80: 408-17.
    PubMedGoogle Scholar
  • 7 Capron L, Jarnet J, Heudes D, Joseph-Monrose D, Bruneval P. Repeated balloon injury of rat aorta: A model of neointima with attenuated inhibition by heparin. Arterioscler Thromb Vasc Biol 1997; 17: 1649-56.
    CrossrefPubMedGoogle Scholar
  • 8 Wilcox JN, Smith KM, Schwartz SM, Gordon D. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci USA 1989; 86: 2839-43.
    CrossrefPubMedGoogle Scholar
  • 9 Marmur JD, Thiruvikraman SV, Fyfe BS, Guha A, Sharma SK, Ambrose A, Fallon JT, Nemerson Y, Taubman MB. Identification of active tissue factor in human coronary atheroma. Circulation 1996; 94: 1226-32.
    CrossrefPubMedGoogle Scholar
  • 10 Kato K, Elsayed YA, Namoto M, Nakagawa K, Sueishi K. Enhanced expression of tissue factor activity in the atherosclerotic aortas of cholesterolfed rabbits. Thromb Res 1996; 82: 335-47.
    CrossrefPubMedGoogle Scholar
  • 11 Hatakeyama K, Asada Y, Marutsuka K, Sato Y, Kamikubo Y, Sumiyoshi A. Localization and Activity of Tissue Factor in Human Aortic Atherosclerotic Lesions. Atherosclerosis 1997; 133: 213-9.
    CrossrefPubMedGoogle Scholar
  • 12 Broze GJ. Tissue factor pathway inhibitor. Thromb Haemost 1995; 74: 90-3.
    PubMedGoogle Scholar
  • 13 Kisanuki A, Asada Y, Hatakeyama K, Hayashi T, Sumiyoshi A. Contribution of the endothelium to intimal thickening in normocholesterolemic and hypercholesterolemic rabbits. Arterioscler Thromb 1992; 12: 1198-205.
    CrossrefPubMedGoogle Scholar
  • 14 Asada Y, Kisanuki A, Tsuneyoshi A, Marutsuka K, Hatakeyama K, Sumiyoshi A. Effects of inflation pressure of balloon catheter on vascular injuries and subsequent development of intimal hyperplasia in rabbit aorta. Atherosclerosis 1996; 121: 45-53.
    CrossrefPubMedGoogle Scholar
  • 15 Haskel EJ, Torr SR, Day KC, Palmier MO, Wun T-C, Sobel BE, Abendschein DR. Prevention of arterial reocclusion after thrombolysis with recombinant lipoprotein-associated coagulation inhibitor. Circulation 1991; 84: 821-7.
    CrossrefPubMedGoogle Scholar
  • 16 Abendschein DR, Meng YY, Torr-Brown S, Sobel BE. Maintenance of coronary patency after fibrinolysis with tissue factor pathway inhibitor. Circulation 1995; 92: 944-9.
    CrossrefPubMedGoogle Scholar
  • 17 Lefkovits J, Malycky JL, Rao JS, Hart CE, Plow EF, Topol EJ, Nicolini FA. Selective inhibition of factor Xa is more efficient than factor VIIa-tissue factor complex blockade at facilitating coronary thrombolysis in the canine model. J Am Coll Cardiol 1996; 28: 1858-65.
    CrossrefPubMedGoogle Scholar
  • 18 Abumiya T, Enjyoji K, Kokawa T, Kamikubo Y, Kato H. An anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody recognized the third Kunitz domain (K3) of free-from TFPI but not lipoprotein-associated forms in plasma. J Biochem 1995; 118: 178-82.
    CrossrefPubMedGoogle Scholar
  • 19 Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992; 326: 242-50.
    CrossrefPubMedGoogle Scholar
  • 20 Davies MJ. The contribution of thrombosis to the clinical expression of coronary atherosclerosis. Thromb Res 1996; 82: 1-32.
    CrossrefPubMedGoogle Scholar
  • 21 Groves HM, Kinlough-Rathbone RL, Richardson M, Jørgensen L, Moore S, Mustard JF. Thrombin generation and fibrin formation following injury to rabbit neointima: studies of vessel wall reactivity and platelet survival. Lab Invest 1982; 46: 605-12.
    PubMedGoogle Scholar
  • 22 Jørgensen L, Grøthe AG, Groves HM, Kinlough-Rathbone RL, Richardson M, Mustard JF. Distribution of cellular responses in rabbit aortae following one and two injuries with a balloon catheter. Br J Exp Pathol 1988; 69: 351-65.
    PubMedGoogle Scholar
  • 23 Jørgensen L, Grøthe AG, Groves HM, Kinlough-Rathbone RL, Richardson M, Mustard JF. Sequence of cellular responses in rabbit aortae following one and two injuries with a balloon catheter. Br J Exp Pathol 1988; 69: 473-86.
    PubMedGoogle Scholar
  • 24 Winocour PD, Hryhorenko L. Spontaneous diabetes in BB wister rats causes small increase in the early proliferative response of smooth muscle cells in re-injured aortae. Exp Mol Pathol 1995; 63: 161-74.
    CrossrefPubMedGoogle Scholar
  • 25 Annex BH, Denning SM, Channon KM, Sketch Jr MH, Stack RS, Morrissey JH, Peters KG. Differential expression of tissue factor protein in directional atherectomy specimens from patients with stable and unstable coronary syndromes. Circulation 1995; 91: 619-22.
    CrossrefPubMedGoogle Scholar
  • 26 Thiruvikraman SV, Guha A, Roboz J, Taubman MB, Nemerson Y, Fallon JT. In situ localization of tissue factor in human atherosclerotic plaques by binding of digoxigenin-labeled factors VIIa and X. Lab Invest 1996; 75: 451-61.
    PubMedGoogle Scholar
  • 27 Ardissino D, Merlini PA, Ariëns R, Coppola R, Bramucci E, Mannucci PM. Tissue-factor antigen and activity in human coronary atherosclerotic plaques. Lancet 1997; 349: 769-71.
    CrossrefPubMedGoogle Scholar
  • 28 Farb A, Burke AP, Tang AL, Liang Y, Mannan P, Smialek J, Virmani R. Coronary plaque erosion without rupture into a lipid core: A frequent cause of coronary thrombosis in sudden coronary death. Circulation 1996; 93: 1354-63.
    CrossrefPubMedGoogle Scholar
  • 29 Davies MJ, Woolf N, Rowles PM, Pepper J. Morphology of the endothelium over atherosclerotic plaques in human coronary arteries. Br Heart J 1988; 60: 459-64.
    CrossrefPubMedGoogle Scholar
  • 30 Van der Wal AC, Becker AE, van der Loos CM, Das PK. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the domain plaque morphology. Circulation 1994; 89: 36-44.
    CrossrefPubMedGoogle Scholar
  • 31 Hatakeyama K, Asada Y, Marutsuka K, Sato Y, Sumiyoshi A. Expression of tissue factor in atherosclerotic lesions. Atherosclerosis 1997; 134: 250-51 (Abstract).
    PubMedGoogle Scholar
  • 32 Ragosta M, Gimple LW, Gertz SD, Dunwiddie CT, Vlasuk GP, Haber HL, Powers ER, Roberts WC, Sarembock IJ. Specific factor Xa inhibition reduces restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits. Circulation 1994; 89: 1262-71.
    CrossrefPubMedGoogle Scholar
  • 33 Sarembock IJ, Gertz SD, Gimple LW, Owen RM, Powers ER, Roberts WC. Effectiveness of recombinant desulfatohirudin in reducing restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits. Circulation 1991; 84: 232-43.
    CrossrefPubMedGoogle Scholar
  • 34 Gerdes C, Faber-Steinfeld V, Yalkinoglu Ö, Wohlfeil S. Comparison of the effects of the thrombin inhibitor r-hirudin in four animal models of neointima formation after arterial injury. Arterioscler Thromb Vasc Biol 1996; 16: 1306-11.
    CrossrefPubMedGoogle Scholar
  • 35 Abendschein DR, Recchia D, Meng YY, Oltrona L, Wickline SA, Eisenberg PR. Inhibition of thrombin attenuates stenosis after arterial injury in minipigs. J Am Coll Cardiol 1996; 28: 1849-55.
    CrossrefPubMedGoogle Scholar
  • 36 Jang Y, Guzman LA, Lincoff AM, Gottsauner-Wolf M, Forudi F, Hart CE, Courtman DW, Ezban M, Ellis SG, Topol EJ. Influence of blockade at specific levels of the coagulation cascade on restenosis in a rabbit atherosclerotic femoral artery injury model. Circulation 1995; 92: 3041-50.
    CrossrefPubMedGoogle Scholar
  • 37 Oltrona L, Speidel CM, Recchia D, Wickline SA, Eisenberg PR, Abendschein DR. Inhibition of tissue factor-mediated coagulation markedly attenuates stenosis after balloon-induced arterial injury in minipigs. Circulation 1997; 96: 646-52.
    CrossrefPubMedGoogle Scholar
  • 38 Smith EB, Thompson WD. Fibrin as a factor in atherogenesis. Thromb Res 1994; 73: 1-19.
    CrossrefPubMedGoogle Scholar
  • 39 Turpie AGG, Weitz JI, Hirsh J. Advances in antithrombotic therapy: novel agents. Thromb Haemost 1995; 74: 565-71.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Sato Y, Asada Y, Marutsuka K, Hatakeyama K, Kamikubo Y, Sumiyoshi A. Tissue factor pathway inhibitor inhibits aortic smooth muscle cell migration induced by tissue factor / factor VIIa complex. Thromb Haemost 1997; 78: 1138-41.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Kamikubo Y, Nakahara Y, Takemoto S, Hamuro T, Miyamoto S, Funatsu A. Human recombinant tissue-factor pathway inhibitor prevents the proliferation of cultured human neonatal aortic smooth muscle cells. FEBS Lett 1997; 407: 116-20.
    CrossrefPubMedGoogle Scholar
  • 42 Schwartz CJ, Valente AJ, Kelley JL, Sprague EA, Edwards EH. Thrombosis and the development of atherosclerosis: Rokitansky revised. Semin Thromb Hemost 1988; 14: 189-95.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Schwartz RS, Holmes Jr DR, Topol EJ. The restenosis paradigm revisited: An alternative proposal for cellular mechanisms. J Am Coll Cardiol 1992; 20: 1284-93.
    CrossrefPubMedGoogle Scholar
  • 44 Zahger D, Fishbein MC, Garfinkel LI, Shah PK, Forrester JS, Regnstrom J, Yano J, Cercek B. VCL, an antagonist of the platelet GPIb receptor, markedly inhibits platelet adhesion and intimal thickening after balloon injury in the rat. Circulation 1995; 92: 1269-73.
    CrossrefPubMedGoogle Scholar