Download PDF
Thromb Haemost 2001; 86(02): 636-639
DOI: 10.1055/s-0037-1616098
Review Article
Schattauer GmbH

Fibrinolysis/Proteolysis Balance in Stable Angina Pectoris in Relation to Angiographic Findings

J. A. Páramo
1   Atherosclerosis Research Unit, Division of Cardiovascular Pathophysiology and Biochemistry
,
J. Orbe
1   Atherosclerosis Research Unit, Division of Cardiovascular Pathophysiology and Biochemistry
,
J. Fernández
2   University Clinic, School of Medicine, University of Navarra, Pamplona, Spain
› Author Affiliations
Further Information

Publication History

Received 18 July 2000

Accepted after resubmission 28 February 2001

Publication Date:
12 December 2017 (online)

    Permissions and Reprints

Summary

The plasma fibrinolytic/proteolytic balance was assessed in 60 stable angina patients who underwent control coronary catheterization and the results were correlated with angiographic findings and control samples (n = 20). The concentrations of t-PA, PAI-1, collagenase (MMP-1), tissue inhibitor of MMP (TIMP-1), plasmin-antiplasmin (PAP) complexes and α2-macroglobulin (α2-M) were measured in plasma samples. The results showed a significant increase of PAP (p <0.001) and a reduction of α2-M (p <0.001) in the group of patients when compared to controls, indicating a degree of fibrinolysis/proteolysis activation. There was no correlation between the different parameters analyzed and the extent of angiographically proven atherosclerosis (one or more stenotic vessels), while the t-PA levels were significantly elevated (p <0.03) in patients with coronary stenosis ≥75% or occlusion. We conclude that there is a disturbance of the plasma fibrinolysis/ proteolysis in patients with stable angina not related to the extent of atherosclerosis. The t-PA levels may be a good marker for coronary occlusion in these patients.

Keywords

Fibrinolysis - proteolysis - coronary disease - t-PA
 

  • References

  • 1 Collen D. The plasminogen (fibrinolytic) system. Thromb Haemost 1999; 82: 259-70.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Nagase H, Woessner JF. Matrix metalloproteinases. J Biol Chem 1999; 274: 21491-4.
    CrossrefPubMedGoogle Scholar
  • 3 Galis ZS. Metalloproteases in remodelling of vascular extracellular matrix. Fibrinolysis 1999; 13: 54-63.
    PubMedGoogle Scholar
  • 4 Borth W. α2-Macroglobulin. A multifunctional binding and targeting protein with possible roles in immunity and autoimmunity. Ann N Y Acad Sci, USA 1999; 878: 267-72.
    PubMedGoogle Scholar
  • 5 Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix-degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 1994; 94: 2493-503.
    CrossrefPubMedGoogle Scholar
  • 6 Barret AJ, Starkey PM. The interaction of α2-macroglobulin with protein-ases: characteristics and specificity of the reaction, and a hypothesis concerning its molecular mechanism. Biochem J 1973; 133: 709-24.
    CrossrefPubMedGoogle Scholar
  • 7 Denis LJ, Verweij J. Matrix metalloproteinase inhibitors: present achievements and future prospects. Investigational New Drugs 1997; 15: 175-85.
    CrossrefPubMedGoogle Scholar
  • 8 Fabunmi RP, Sukhova GK, Sugiyama S, Libby P. Expression of tissue inhibitor of metalloproteinases-3 in human atheroma and regulation in esion associated cells. A potential protective mechanism in plaque stability. Circ Res 1998; 83: 270-8.
    CrossrefPubMedGoogle Scholar
  • 9 Prescott MF, Sawyer WK, von Linden-Reed J, Jeune M, Chou M, Caplan SL, Jeng AY. Effect of matrix metalloproteinase inhibition on progression of atherosclerosis and aneurysm in LDL receptor-deficient mice over-expressing MMP-3, MMP-12, and MMP 13 and on restenosis in rats after balloon injury. Ann NY Acad Sci 1999; 878: 179-90.
    CrossrefPubMedGoogle Scholar
  • 10 Carmeliet P, Moons L, Lijnen HR, Baes M, Lemaître V, Tipping P, Drew A, Eeckout Y, Shapiro S, Lupu F, Collen D. Urokinase-generated plasmin is a candidate activator of matrix metalloproteinases during atherosclerotic aneurysm formation. Nature Gen 1997; 17: 439-44.
    CrossrefPubMedGoogle Scholar
  • 11 Lijnen HG, Van Hoef BV, Lupu F, Moons L, Carmeliet P, Collen D. Function of the plasminogen/plasmin and matrix metalloproteinase systems after vascular injury in mice with targeted inactivation of fibrinolytic system genes. Arterioscler Thromb Vasc Biol 1998; 18: 1035-45.
    CrossrefPubMedGoogle Scholar
  • 12 Lijnen HR. Molecular interactions between the plasminogen/plasmin and matrix metalloproteinase systems. Fibrinol Proteol 2000; 14: 175-81.
    CrossrefPubMedGoogle Scholar
  • 13 Páramo JA, Panizo C, Montes R, Orbe J, Alegría E, Martínez-Caro D, Dooijewaard G. Markers of fibrinolytic potency and clotting activation in stable angina pectoris: role of urokinase, assessment of atrioventricular differences and correlation with coronary patency. Fibrinol Proteol 1999; 13: 133-8.
    CrossrefPubMedGoogle Scholar
  • 14 Kai H, Ikeda H, Yasukawa H, Saki Y, Kuwahara F, Ueno T, Sugi K, Imaizumi T. Peripheral blood levels of matrix metalloproteinases-2 and-9 are elevated in patients with acute coronary syndromes. J Am Coll Cardiol 1998; 32: 368-72.
    CrossrefPubMedGoogle Scholar
  • 15 Korninger C, Speizer W, Wojta J, Binder RR. Sandwich ELISA for t-PA antigen employing a monoclonal antibody. Thromb Res 1983; 31: 427-36.
    CrossrefPubMedGoogle Scholar
  • 16 Páramo JA, Alfaro MJ, Rocha E. Postoperative changes in the plasmatic levels of tissue-type plasminogen activator and its fast-acting inhibitor: relationship to deep venous thrombosis and influence of prophylaxis. Thromb Haemost 1985; 54: 713-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Montes R, Páramo JA, Anglés-Cano E, Rocha E. Development and clinical application of a new ELISA assay to deterfmine plasmin-α2-Antiplasmin complexes in plasma. Br J Haematol 1996; 92: 979-85.
    CrossrefPubMedGoogle Scholar
  • 18 López Y, Paloma MJ, Rifón J, Cuesta B, Páramo JA. Measurement of prethrombotic markers in the assessment of acquired hypercoagulable states. Thromb Res 1999; 93: 71-8.
    CrossrefPubMedGoogle Scholar
  • 19 Mohacsi AT, Fulop B, Kozlovsky M, Hanck M, Kiss I, Leovey A. Sera and leukocyte elastase-type protease and antiprotease activity in healthy and atherosclerotic subjects of various ages. J Gerontol 1992; 47: 154-8.
    PubMedGoogle Scholar
  • 20 Chu CT, Howard GC, Pizzo SV. α2-Macroglobulin: a sensor for proteolysis. Ann NY Acad Sci, USA 1999; 878: 291-307.
    PubMedGoogle Scholar
  • 21 Oleksyszyn J, Augustine AJ. Plasminogen modulation of IL-1-stimulated degradation in bovine and human articular cartilage explants. The role of the endogenous inhibitors, PAI-1, aspha-2-antiplasmin, alpha-1-PI, alpha-2-macroglobulin and TIMP. Inflammation Res 1996; 45: 464-72.
    CrossrefPubMedGoogle Scholar
  • 22 Thompson SG, Kienast J, Pyke SDM, Haverkate F, va de Loo JLW. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995; 332: 635-41.
    CrossrefPubMedGoogle Scholar
  • 23 Ridker PM, Vaughan DE, Stampfer MJ, Manson JE, Hennekens CH. Endogenous tissue-type plasminogen activator and risk of myocardial infarction. Lancet 1993; 341: 1165-8.
    CrossrefPubMedGoogle Scholar
  • 24 Ridker PM, Hennekens CM, Stampfer MJ, Manson JE, Vaughan DE. Prospective study of endogenous tissue plasminogen activator and risk of stroke. Lancet 1994; 343: 940-3.
    CrossrefPubMedGoogle Scholar
  • 25 Brown DL, Hibbs MS, Kearney M, Loushin C, Isner JM. Identification of 92-kd gelatinase in human coronary atherosclerotic lesions. Association of active enzyme synthesis with unstable angina. Circulation 1995; 92: 1565-9.
    PubMedGoogle Scholar
  • 26 Shah PK, Falk E, Badimon JJ, Fernández-Ortiz AF, Mailhac A, Villarreal-Levy G. et al. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix degrading metalloproteinases and implications for plaque rupture. Circulation 1995; 92: 1565-9.
    PubMedGoogle Scholar
  • 27 Galis ZS, Sukhova GK, Libby P. Microscopic localization of active proteases by in situ zymography: detection of metalloproteinase activity in vascular tissue. FASEB J 1995; 9: 974-80.
    CrossrefPubMedGoogle Scholar
  • 28 Marathe S, Kuriakose G, Williams KJ, Tabas I. Sphingomyelinase, an enzyme implicated in atherogenesis, is present in atherosclerotic lesions and binds to specific components of the subendothelial extracellular matrix. Arterioscler Thromb Vasc Biol 1999; 19: 2648-58.
    CrossrefPubMedGoogle Scholar