Thromb Haemost 1999; 82(S 01): 4-7
DOI: 10.1055/s-0037-1615544
Commentaries
Schattauer GmbH

A Role of Plasminogen in Atherosclerosis and Restenosis Models in Mice

Edward F. Plow
1   From the Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Foundation, Cleveland, OH
,
Victoria A. Ploplis
2   W. M. Keck Transgene Center, Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN
,
Steven Busuttil
3   Cleveland Veterans Administration Medical Center, Section of Vascular Surgery, Cleveland, OH, USA
,
Peter Carmeliet
4   Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute of Biotechnology, University of Leuven, Leuven, Belgium
,
Desire Collen
4   Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute of Biotechnology, University of Leuven, Leuven, Belgium
› Author Affiliations
Further Information

Publication History

Publication Date:
14 December 2017 (online)

Summary

In addition to its preeminent role in fibrinolysis, the plasminogen system is believed to play a key role in mediating cell migration. Leukocyte migration into the vessel wall is a key and early event in the development of the lesions of atherosclerosis and restenosis, pathologies which may be viewed as specific examples of vascular inflammatory responses. The development of mice in which the plasminogen gene has been inactivated affords an opportunity to test the contribution of plasminogen in leukocyte migration during in vivo. This article summarizes recent studies conducted in murine models of the inflammatory repsonse, restenosis and atherosclerosis in which leukocyte migration, and in particular monocyte/macrophage migration, has been evaluated in plasminogen-deficient mice. Recruitment of these cells through the vessel wall in inflammatory response models and into the vessel wall in restenosis and transplant atherosclerosis models is substantially blunted. These data implicate plasminogen in the migration of leukocytes in these murine models. With the numerous correlations between components and/or activation of the plasminogen system in restenosis and atherosclerosis, these results also support a role of plasminogen in the corresponding human pathologies.

 
  • References

  • 1 Libby P, Schwartz Tanaka DE, Brogi E, Tanaka H, Clinton SK. A cascade model for restenosis. A special case of atherosclerotic progression. Circulation 1991; 86: 47-52.
  • 2 Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362: 801-9.
  • 3 Katsuda S, Boyd HC, Fligner C, Ross R, Gown AM. Human atherosclerosis. III. Immunocytochemical analysis of the cell composition of lesions of young adults. Am J Pathol 1992; 140: 907-10.
  • 4 Assoian RK, Fleurdelis BZ, Stevenson HC, Miller PJ, Madtes DK, Raines EW, Ross R, Sporn MB. Expression and secretion of type beta transforming growth factor by activated human macrophages. Acad Sci USA 1987; 84: 6020-4.
  • 5 Porreca A, DiFebbo C, Reale M, Castellani ML, Baccante G, Barbacane R, Conti P, Cuccurullo F, Poggi A. Monocyte chemotactic protein, (MCP-1) is a mitogen for cultured rat vascular smooth muscle cells. J Vasc Res 1997; 34: 58-65.
  • 6 Saksela O, Rifkin DB. Cellassociated plasminogen activation: Regulation and physiological functions. Annu Rev Cell Biol 1988; 4: 93-126.
  • 7 Plow EF, Herren T, Redlitz A, Miles LA, Hoover-Plow JL. The cell biology of the plasminogen system. FASEB J 1995; 9: 939-45.
  • 8 Dano K, Behrendt N, Brunner N, Ellis V, Ploug M, Dyke C. The urokinase receptor: protein structure and role in plasminogen activation and cancer invasion. Fibrinolysis 1994; 8: 189-203.
  • 9 Chapman Jr. HA, Vavrin Z, Hibbs Jr. JB. Macrophage fibrinolytic activity: Identification of two pathways of plasmin formation by intact cells and of a plasminogen activator inhibitor. Cell 1982; 28: 653-62.
  • 10 Hart PH, Vitti GF, Burgess DR, Singleton DK, Hamilton JA. Human monocytes can produce tissue-type plasminogen activator. J Exp Med 1989; 169: 1509-14.
  • 11 Vassalli J, Dayer J, Wohlwend A, Belin D. Concomitant secretion of prourokinase and of a plasminogen activator specific inhibitor by cultured human monocytes-macrophages. J Exp Med 1984; 159: 1653.
  • 12 Hart PH, Burgess DR, Vitti GF, Hamilton JA. Interleukin-4 stimulated human monocytes to produce tissue-type plasminogen activator. Blood 1989; 74: 1222-5.
  • 13 Vassalli JD, Baccino D, Belin D. A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase. J Cell Biol 1985; 100: 86-92.
  • 14 Plow EF, Freaney DE, Plescia J, Miles LA. The plasminogen system and cell surfaces: Evidence for plasminogen and urokinase receptors on the same cell type. J Cell Biol 1986; 103: 2411-20.
  • 15 Felez J, Miles LA, Plescia J, Plow EF. Regulation of plasminogen receptor expression on human monocytes and monocytoid cell lines. J Cell Biol 1990; 111: 1673-83.
  • 16 Felez J, Chanquia CJ, Levin EG, Miles LA, Plow EF. Binding of tissue plasminogen activator to human monocytes and monocytoid cells. Blood 1991; 78: 2318-27.
  • 17 Bugge TH, Flick MJ, Daugherty CC, Degen JL. Plasminogen deficiency causes severe thrombosis but is compatible with development and reproduction. Genes Dev 1995; 9: 794-807.
  • 18 Ploplis VA, Carmeliet P, Vazirzadeh S, Van Vlaenderen I, Moons L, Plow EF, Collen D. Effects of disruption of the plasminogen gene in mice on thrombosis, growth and health. Circulation 1995; 92: 2585-93.
  • 19 Carmeliet P, Collen D. Gene manipulation of the plasminogen and coagulation system in mice. Semin Thromb Haemost 1996; 22: 525-42.
  • 20 Carmeliet P, Collen D. Genetic analysis of the plasminogen and coagulation system in mice. Haemostasis 1996; 26 (Suppl. 4) 132-53.
  • 21 Carmeliet P, Moons L, Lijnen R, Baes M, Lemaitre V, Tipping P, Drew A, Eeckhout Y, Shaprio S, Lupu F, Collen D. Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation. Nature Genet 1997; 17: 439-44.
  • 22 Carmeliet P, Moons L, Herbert JM, Crawley J, Lupu F, Lijnen R, Collen D. Urokinase but not tissue plasminogen activator mediates arterial neointima formation in mice. Circ Res 1997; 81: 829-39.
  • 23 Herbert JM, Carmeliet P. Urokinase mediates bFGF-induced vascular smooth muscle cell migration under the control of TGFp. Fibrinolysis Proteolysis 1998; 12: 89-96.
  • 24 Hopper KE. Kinetics of macrophage recruitment and turnover in peritoneal inflammatory exudates induced by Salmonella or thioglycollate broth. J Leukoc Biol 1986; 39: 435-46.
  • 25 Hurley JV, Ryan GB, Friedman A. The mononuclear response to intrapleural injection in the rat. J Pathol Bacteriol 1966; 91: 575-87.
  • 26 Rodrick ML, Lamster IB, Sonis ST, Pender SG, Kolodkin AB, Fitzgerald JE, Wilson RE. Effects of supernatants of polymorphonuclear neutrophils recruited by different inflammatory substances on mitogen responses of lymphocytes. Inflammation. 1982 6. 111.
  • 27 Ploplis VA, French EL, Carmeliet P, Collen D, Plow EF. Plasminogen deficiency differentially affects recruitment of inflammatory cell populations in mice. Blood 1998; 91: 2005-9.
  • 28 Ploplis V, Busuttil S, French E, Tang L, Carmeliet P, Collen D, Plow E. The inflammatory response to biopolymer implants in plasminogen deficient mice. [Abstract] Thromb Haemost. 1997 (Suppl.) PS2234.
  • 29 Tang L, Eaton JW. Inflammatory responses to biomaterials. Am J Clin Pathol 1995; 103: 466-71.
  • 30 Lindner V, Fingerle J, Reidy MA. Mouse model of arterial injury. Circ Res 1993; 73: 792-6.
  • 31 Rudic RD, Shesely EG, Maeda N, Smithes O, Segal SS, Sessa WC. Direct evidence for the importance of endothelium-derived nitro oxide in vascular remodeling. J Clin Invest 1998; 101: 731-6.
  • 32 Carmeliet P, Moons L, Stassen JM, De Mol M, Bouche A, Van den, Oord JJ, Kockx M, Collen D. Vascular wound healing and neointima formation induced by perivascular electric injury. Am J Pathol 1997; 150: 761-76.
  • 33 Carmeliet P, Moons L, Ploplis V, Plow E, Collen D. Impaired arterial neointima formation in mice with disruption of the plasminogen gene. J Clin Invest 1997; 99: 200-8.
  • 34 Schwartz CJ, Valente AJ, Kelley JL, Sprague EA, Edwards EH. Thrombosis and the development of atherosclerosis: Rokitansky revisited. Semin Thromb Haemost 1988; 14: 189-95.
  • 35 Mozes G, Mohacsi T, Gloviczki P, Menawat S, Kullo I, Spector D, Taylor J, Crotty TB, O'Brien T. Adenovirus-mediated gene transfer of macrophage colony stimulating factor to the arterial wall in vivo. Arterioscler Thromb Vasc Biol 1998; 18: 1157-63.
  • 36 Moons L, Shi C, Ploplis V, Plow E, Haber E, Collen D, Carmeliet P. Reduced transplant arteriosclerosis in plasminogen-deficient mice. J Clin Invest 1998; 102: 1788-97.
  • 37 Xiao Q, Danton MJS, Witte DP, Kowala MC, Valentine MT, Bugge TH, Degen JL. Plasminogen deficiency accelerates vessel wall disease in mice predisposed to atherosclerosis. Proc Natl Acad Sci USA 1997; 94: 10335-40.
  • 38 Shi C, Russell ME, Bianchi C, Newell JB, Haber E. Murine model of accelerated transplant arteriosclerosis. Circ Res 1994; 75: 199-207.
  • 39 Tang L, Ugarova TP, Plow EF, Eaton JW. Molecular determinants of acute inflammatory responses to biomaterials. J Clin Invest 1996; 97: 1329-34.
  • 40 Xiao Q, Danton MJS, Witte DP, Kowala MC, Valentine MT, Degen JL. Fibrinogen deficiency is compatible with the development of atherosclerosis in mice. J Clin Invest 1998; 101: 1184-94.
  • 41 Khalil N, Corne S, Whitman C, Yacyshyn T. Plasmin regulates the activation of cell-associated latent TGFp secreted by rat alveolar macrophages after in vivo bleomycin injury. Am J Respir Cell Mol Biol 1996; 15: 252-9.
  • 42 Syrovets T, Tippler B, Rieks M, Simmet T. Plasmin is a potent and specific chemoattractant for human peripheral monocytes acting via a cyclic guanosine monophosphate-dependent pathway. Blood 1997; 89: 4574-83.