Lauricella, A.M.; Quintana, I.; Castañon, M.; Sassetti, B.; Kordich, L. "Influence of homocysteine on fibrin network lysis" (2006) Blood Coagulation and Fibrinolysis. 17(3):181-186
Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor


To elucidate some of the links between homocysteine and vascular disease, we have evaluated the effect of the amino acid on the formation (by kinetics studies), structure (by electron microscopy) and lysis of the fibrin network, using tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). We have studied whether homocysteine could alter the activity of the components involved in fibrinolysis (by amidolytic and thrombolytic methods). The results showed that homocysteine-associated networks were more compact and branched than controls (52 ± 6 vs 44 ± 5 fibers/field, P = 0.008), and were formed by shorter and thicker fibers. This clot proved to be more resistant to fibrinolysis with u-PA than control [lysis time 50%: 257 ± 16 (homocysteine) vs 187 ± 6 min (control); P < 0.004], but there were no differences with t-PA. Homocysteine did not affect the biological activities of plasmin, or plasminogen activation by t-PA and u-PA. Defective fibrinolysis with u-PA was therefore associated with homocysteine-fibrin structural alterations rather than the homocysteine effect on the biological activities of the fibrinolytic components evaluated. Results suggest that hyperhomocysteinemic patients could produce tight clots, were more resistant to lysis, and generated a procoagulant environment in situ. We believe that our findings may contribute to understanding the mechanisms involved in the homocysteine harmful effect. © 2006 Lippincott Williams & Wilkins.


Documento: Artículo
Título:Influence of homocysteine on fibrin network lysis
Autor:Lauricella, A.M.; Quintana, I.; Castañon, M.; Sassetti, B.; Kordich, L.
Filiación:Department of Biological Chemistry, School of Exact and Natural Sciences, Buenos Aires University, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas Y Naturales, Ciudad Universitaria, (C1428EHA) Buenos Aires, Argentina
Palabras clave:Fibrin networks; Fibrinolysis; Homocysteine; fibrin; homocysteine; plasminogen; tissue plasminogen activator; urokinase; amino acid analysis; article; binding kinetics; controlled study; electron microscopy; fiber; fibrin metabolism; genetic resistance; human; human cell; hyperhomocysteinemia; lysis; plasminogen activation; priority journal; regulatory mechanism; thickness; vascular disease; Blood Coagulation; Fibrin; Fibrinolysis; Homocysteine; Humans; Microscopy, Electron; Plasma; Plasmin; Plasminogen Activator Inhibitor 1; Plasminogen Activators; Plasminogen Inactivators
Página de inicio:181
Página de fin:186
Título revista:Blood Coagulation and Fibrinolysis
Título revista abreviado:Blood Coagul. Fibrinolysis
CAS:fibrin, 9001-31-4; homocysteine, 454-28-4, 6027-13-0; plasminogen, 9001-91-6; tissue plasminogen activator, 105913-11-9; urokinase, 139639-24-0; Fibrin, 9001-31-4; Homocysteine, 454-28-4; Plasmin, EC; Plasminogen Activator Inhibitor 1; Plasminogen Activators, EC 3.4.21.-; Plasminogen Inactivators


  • Bertina, R.M., Molecular risk factor for thrombosis (1999) Thromb Haemost, 82, pp. 601-609
  • Guba, S., Fonseca, V., Fink, L., Hyperhomocysteinemia and thrombosis (1999) Semin Thromb Hemost, 25, pp. 291-309
  • D'Angelo, A., Selhub, J., Homocysteine and thrombotic disease (1997) Blood, 90, pp. 1-11
  • Van Guldener, C., Stehouwer, C., Hyperhomocysteinemia, vascular pathology and endothelial dysfunction (2000) Semin Thromb Hemost, 26, pp. 313-324
  • Welch, G.N., Loscalzo, J., Homocysteine and atherothrombosis (1998) N Engl J Med, 338, pp. 1042-1050
  • Mujumdar, V., Aru, G., Tgagi, S., Induction of oxidative stress by homocyst(e)ine impairs endothelial function (2001) J Cell Biochem, 82, pp. 491-500
  • Coppola, A., Giovanni, D., De Stefano, V., Mancini, F., Cerbone, A., Di Minno, G., Homocysteine, coagulation, platelet function, and thrombosis (2000) Semin Thromb Hemost, 26, pp. 243-254
  • Ueland, M., Homocysteine species as components of plasma redox thiol status (1995) Clin Chem, 41, pp. 340-342
  • Lauricella, A.M., Quintana, I., Kordich, L., Effects of homocysteine thiol group on fibrin networks: Another possible mechanism of harm (2002) Thromb Res, 107, pp. 75-79
  • Sauls, D.L., Wolberg, A.S., Hoffman, M., Elevated plasma homocysteine leads to alterations in fibrin clot structure and stability: Implications for the mechanism of thrombosis in hyperhomocysteinemia (2003) J Thromb Haemost, 1, pp. 300-306
  • Graham, I.M., Daly, L.E., Refsum, H.M., Robinson, K., Brattstrom, L.E., Ueland, P.M., Plasma homocysteine as a risk factor for vascular disease: The European Concerted Action Project (1997) JAMA, 277, pp. 1775-1781
  • Vollset, S.E., Refsum, H., Irgens, L.M., Emblem, B.M., Tverdal, A., Gjessing, H.K., Plasma total homocysteine, pregnancy complications, and adverse pregnancy outcomes: The Hordaland Homocysteine study (2000) Am J Clin Nutr, 71, pp. 962-968
  • Miller, J.W., Homocysteine and Alzheimer's disease (1999) Nutr Rev, 57, pp. 126-129
  • Boushey, C.J., Beresford, S.A.A., Omenn, G.S., Motulsky, A.G., A quantitative assessment of plasma homocysteine as a risk for vascular disease: Probable benefits of increasing folic acid intake (1995) JAMA, 274, pp. 1049-1057
  • Clarke, R., Armitage, J., Vitamin supplements and cardiovascular risk: Review of the randomised trials and homocysteine-lowering vitamin supplements (2000) Semin Thromb Hemost, 26, pp. 341-348
  • Smilde, T., Van Den Berkmortel, F., Boerts, G.H., Wollersheim, H., De Boo, T., Van Langen, Carotid and femoral artery wall thickness in patients at risk for cardiovascular disease, with emphasis on hyperhomocysteinemia (1998) Arterioscler Thromb Vasc Biol, 18, pp. 1958-1963
  • Lambert, J., Van Der Berg, M., Steyn, M., Rauwerda, J.A., Donker, A.J., Stehouwer, C.D., Familial hyperhomocysteinaemia and endothelium-dependent vasodilation and arterial distensibility of large arteries (1999) Cardiovasc Res, 42, pp. 743-751
  • Poddar, R., Sivasubramanian, N., Di Bello, P.M., Robinson, K., Jacobsen, D.W., Homocysteine induces expression and secretion of monocyte chemottractant protein-1 and interleukin-8 in human aortic endothelial cells: Implications for vascular disease (2001) Circulation, 103, pp. 2717-2723
  • Weiss, N., Mechanisms of increased vascular oxidant stress in hiperhomocysteinemia and its impact on endothelial function (2005) Curr Drug Metab, 6, pp. 27-36
  • Weisel, J., Veklich, Y., Collet, J., Francis, C., Structural studies of fibrinolysis by electron and light microscopy (1999) Thromb Haemost, 82, pp. 277-282
  • Meh, D.A., Mosesson, M.W., DiOrio, J.P., Siebenlist, K.R., Hernandez, I., Amrani, D.L., Stojanovich, L., Desintegration and reorganization of fibrin networks during tissue-type plaminogen activator-induced clot lysis (2001) Blood Coagul Fibrinolysis, 12, pp. 627-637
  • Collet, J.P., Park, D., Lesty, C., Soria, J., Soria, C., Montalescot, G., Influence of fibrin network conformation and fibrin fiber diameter on fibrinolysis speed. Dynamic and structural approaches by confocal microscopy (2000) Arterioscler Thromb Vasc Biol, 20, pp. 1354-1361
  • Wu, J.H., Siddiqui, K., Diamond, S., Transport phenomena and clot dissolving therapy: An experimental investigation of diffusion-controlled and permeation-enheanced fibrinolysis (1994) Thromb Haemost, 72, pp. 105-112
  • Kolev, K., Machovich, R., Molecular and cellular modulation of fibrinolysis (2003) Thromb Haemost, 89, pp. 610-621
  • Carr, M.E., Alving, B.M., Effect of fibrin structure on plasmin-mediated dissolution of plasma clots (1995) Blood Coagul Fibrinolysis, 6, pp. 567-573
  • Gabriel, D.A., Muga, K., Boothroyd, E.M., The effect of fibrin structure in fibrinolysis (1992) J Biol Chem, 267, pp. 24259-24263
  • Collet, J.P., Nagaswami, C., Farrell, D.H., Montalescot, G., Weisel, J.W., Influence of gamma' fibrinogen splice variant on fibrin physical properties and fibrinolysis rate (2004) Arterioscler Thromb Vasc Biol, 24, pp. 382-386
  • Siebenlist, K.R., Mosesson, M.W., Hernandez, I., Bush, L.A., Di Cera, E., Shainoff, J.R., Studies on the basis for the properties of fibrin produced from fibrinogen containing gamma' chains (2005) Blood, 106, pp. 2730-2736
  • Siebenlist, K., Meh, D., Mosesson, M., Protransglutaminase (factor XIII) mediated crosslinking of fibrinogen and fibrin (2001) Thromb Haemost, 86, pp. 1221-1228
  • Tofler, G.H., D'Agostino, R.B., Jacques, P.F., Bostom, A.G., Wilson, P.W.F., Lipinska, I., Association between increased homocysteine levels and impaired fibrinolytic potencial: Potencial mechanism for cardiovascular risk (2002) Thromb Haemost, 88, pp. 799-804
  • Hajjar, K.A., Homocysteine induced modulation of tissue of plasminogen activator binding to its endothelial cell membrane receptor (1993) J Clin Invest, 91, pp. 2873-2879


---------- APA ----------
Lauricella, A.M., Quintana, I., Castañon, M., Sassetti, B. & Kordich, L. (2006) . Influence of homocysteine on fibrin network lysis. Blood Coagulation and Fibrinolysis, 17(3), 181-186.
---------- CHICAGO ----------
Lauricella, A.M., Quintana, I., Castañon, M., Sassetti, B., Kordich, L. "Influence of homocysteine on fibrin network lysis" . Blood Coagulation and Fibrinolysis 17, no. 3 (2006) : 181-186.
---------- MLA ----------
Lauricella, A.M., Quintana, I., Castañon, M., Sassetti, B., Kordich, L. "Influence of homocysteine on fibrin network lysis" . Blood Coagulation and Fibrinolysis, vol. 17, no. 3, 2006, pp. 181-186.
---------- VANCOUVER ----------
Lauricella, A.M., Quintana, I., Castañon, M., Sassetti, B., Kordich, L. Influence of homocysteine on fibrin network lysis. Blood Coagul. Fibrinolysis. 2006;17(3):181-186.