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J. Biol. Chem., Vol. 278, Issue 24, 21331-21335, June 13, 2003

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Dynamic Changes of Fibrin Architecture during Fibrin Formation and Intrinsic Fibrinolysis of Fibrin-rich Clots^*

Jean-Philippe Collet   ¶, Claude Lesty ||, Gilles Montalescot  and John W. Weisel 

From the Institut de Cardiologie Pitié-Salpêtrière Hospital (Assistance Publique), 75013 Paris, France, ^|| Institut de Cardiologie Hematology Laboratory, Pitié-Salpêtrière Hospital (Assistance Publique), 75013 Paris, France, Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Clotting and fibrinolysis are initiated simultaneously in vivo, and fibrinolysis usually occurs without any individualized lysis front (intrinsic fibrinolysis). We have developed a novel model to assess whether morphological changes resulting from intrinsic fibrinolysis are similar to those previously reported at the lysis front using externally applied lytic agents. Fibrin assembly and fibrinolysis were followed in real-time by confocal microscopy using gold-labeled fibrinogen molecules. An increase in fiber absorbance (30%, p < 0.01) and a decrease in fiber diameter (60%, p < 0.01) due to the ongoing accumulation and packing of fibrin molecules were the most significant detectable features occurring during fibrin assembly. Similar features with a similar magnitude were observed during fibrin dissolution, but in the reverse order and with a 3-fold increase in duration. Then, lysing fibers were progressively transected laterally, and thinner fibers were cleaved at a 2.5-fold faster rate than thicker fibers (p < 0.001). Frayed lysing fibers were seen to interact progressively with adjoining fibers (agglomeration), leading to a 76 and 88% increase in the network pore diameter (p < 0.05) and fiber diameter (p < 0.01), respectively. At the maximum decrease in fiber absorbance (46%, p < 0.05), the network suddenly collapsed with the release of large fragments that gradually vanished. Morphological changes of fibrin that occur during intrinsic fibrinolysis are similar as those observed next to the lysis front, although they are not restricted spatially to the clot/surrounding milieu interface but are observed through the entire clot.

Received for publication, December 13, 2002 , and in revised form, March 17, 2003.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed: Inst. de Cardiologie, Centre Hospitalier Universitaire Pitié-Salpêtrière (AP-HP), 47, Boulevard de l'Hôpital, 75013 Paris, France. Tel.: 33-1-42-16-30-07; Fax: 33-1-42-16-29-31; E-mail: jean-philippe.collet{at}psl.ap-hop-paris.fr.

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