Wohner, N and Sotonyi, P and Machovich, R and Szabo, L and Tenekedjiev, K and Silva, MMCG and Longstaff, C and Kolev, K, Lytic resistance of fibrin containing red blood cells, Arteriosclerosis, Thrombosis, and Vascular Biology, 31, (10) pp. 2306-2313. ISSN 1079-5642 (2011) [Refereed Article]
Copyright 2011 American Heart Association, Inc.
Objective: Arterial thrombi contain variable amounts of red blood cells (RBCs), which interact with fibrinogen through an eptifibatide-sensitive receptor and modify the structure of fibrin. In this study, we evaluated the modulator role of RBCs in the lytic susceptibility of fibrin.
Methods and Results: If fibrin is formed at increasing RBC counts, scanning electron microscopy evidenced a decrease in fiber diameter from 150 to 96 nm at 40% (v/v) RBCs, an effect susceptible to eptifibatide inhibition (restoring 140 nm diameter). RBCs prolonged the lysis time in a homogeneous-phase fibrinolytic assay with tissue plasminogen activator (tPA) by up to 22.7±1.6%, but not in the presence of eptifibatide. Confocal laser microscopy using green fluorescent protein–labeled tPA and orange fluorescent fibrin showed that 20% to 40% (v/v) RBCs significantly slowed down the dissolution of the clots. The fluorescent tPA variant did not accumulate on the surface of fibrin containing RBCs at any cell count above 10%. The presence of RBCs in the clot suppressed the tPA-induced plasminogen activation, resulting in 45% less plasmin generated after 30 minutes of activation at 40% (v/v) RBCs.
Conclusion: RBCs confer lytic resistance to fibrin resulting from modified fibrin structure and impaired plasminogen activation through a mechanism that involves eptifibatide-sensitive fibrinogen-RBC interactions.
|Item Type:||Refereed Article|
|Research Division:||Information and Computing Sciences|
|Research Group:||Information systems|
|Research Field:||Decision support and group support systems|
|Objective Division:||Expanding Knowledge|
|Objective Group:||Expanding knowledge|
|Objective Field:||Expanding knowledge in the information and computing sciences|
|UTAS Author:||Tenekedjiev, K (Professor Kiril Tenekedjiev)|
|Web of Science® Times Cited:||82|
|Deposited By:||Governance Office|
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