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Carbon monoxide releasing molecule-2 enhances alpha(2)-antiplasmin activity
Journal article   Peer reviewed

Carbon monoxide releasing molecule-2 enhances alpha(2)-antiplasmin activity

Saninuj N. Malayaman, Jack B. Cohen, Kelly A. Machovec, Brian E. Bernhardt, Matt R. Arkebauer and Vance G. Nielsen
Blood coagulation & fibrinolysis, v 22(4), pp 345-348
01 Jun 2011
PMID: 21330914

Abstract

Hematology Life Sciences & Biomedicine Science & Technology
The objective of this study was to determine whether carbon monoxide releasing molecule (tricarbonyldichlororuthenium (II) dimer, CORM-2) directly affects alpha(2)-antiplasmin activity. For this purpose, purified alpha(2)-antiplasmin was exposed to 0 or 100 mu mol/l CORM-2 for 5 min at 37 degrees C and then placed in alpha(2)-antiplasmin-deficient plasma (25 mu g/ml alpha(2)-antiplasmin and 3.3 mu mol/l CORM-2 final concentrations). In a second series of experiments, alpha(2)-antiplasmin and deficient plasma were combined and then exposed to 0 or 100 mu mol/l CORM-2. Coagulation was activated with tissue factor and fibrinolysis initiated with tissue-type plasminogen activator (n = 8 per condition). Thrombus growth/disintegration kinetics were monitored with thrombelastography until clot lysis time occurred. Samples containing alpha(2)-antiplasmin preexposed to 100 mu mol/l CORM-2 demonstrated no changes in the velocity of clot growth, but had a significant prolongation of the time to maximum rate of lysis, clot lysis time, and a significant decrease in the maximum rate of clot lysis compared with samples preexposed to 0 mu mol/l CORM-2. In sharp contrast, addition of 100 mu mol/l CORM-2 to premixed alpha(2)-antiplasmin in its deficient plasma resulted in significant, marked increases in the velocity of clot growth and the strength with concurrent antifibrinolytic effects as in the first series. In conclusion, CORM-2 exerts its antifibrinolytic effects by direct enhancement of alpha(2)-antiplasmin activity. It appears that combined modification of both fibrinogen and alpha(2)-antiplasmin are responsible for the robust procoagulant/antifibrinolytic effects of CORM-2 in the fibrinolytic environment. Blood Coagul Fibrinolysis 22:345-348 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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