Influence of homocysteine on fibrin network lysis.
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.
Laboratory of Haemostasis and Thrombosis, Department of Biological Chemistry, School of Exact and Natural Sciences, Buenos Aires University, Argentina. lht@qb.fcen.uba.ar
Ana María
AM
Lauricella
Irene
I
Quintana
Mercedes
M
Castañon
Beatriz
B
Sassetti
Lucía
L
Kordich
D001777:Blood Coagulation / Q000502:physiology; D005337:Fibrin / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology*; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D008854:Microscopy, Electron; D010949:Plasma / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010960:Plasminogen Activators / Q000737:chemistry / Q000378:metabolism; D015849:Plasminogen Inactivators / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D015849:Plasminogen Inactivators; D006710:Homocysteine; D005337:Fibrin; D010960:Plasminogen Activators; D005341:Fibrinolysin