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Endothelial Cells Organize Fibrin Clots into Structures That Are More Resistant to Lysis

Published online by Cambridge University Press:  12 May 2005

W. Gray Jerome ,
Stefan Handt  and
Roy R. Hantgan
W. Gray Jerome
Affiliation:
Departments of Pathology and Cancer Biology, U-2206 MCN, Vanderbilt University School of Medicine, Nashville, TN 37232-2561, USA
Stefan Handt
Affiliation:
Institute of Pathology, Aachen University of Technology, D-52072 Aachen, Germany Present address: Institut für Pathologie, Bonn-Duisdorf, Heilsbachstraße 15, D-53123 Bonn, Germany.
Roy R. Hantgan
Affiliation:
Department of Biochemistry, Wake Forest University Health Sciences Center, Winston-Salem, NC 27157, USA
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Abstract

Acute myocardial infarction is a major cause of death and disability in the United States. Introducing thrombolytic agents into the clot to dissolve occlusive coronary artery thrombi is one method of treatment. However, despite advances in our knowledge of thrombosis and thrombolysis, survival rates following thrombolytic therapy have not improved substantially. This failure highlights the need for further study of the factors mediating clot stabilization. Using laser scanning confocal microscopy of clots formed from fluorescein-labeled fibrinogen, we investigated what effect binding of fibrin to the endothelial surface has on clot structure and resistance to lysis. Fluorescent fibrin clots were produced over human umbilical vein endothelial cells (HUVEC) and the clot structure analyzed. In the presence of HUVEC, fibrin near the endothelial surface was more organized and occurred in tighter bundles compared to fibrin just 50 μm above. The HUVEC influence on fibrin architecture was blocked by inhibitory concentrations of antibodies to αV or β3 integrin subunits. The regions of the clots associated with endothelial cells were more resistant to lysis than the more homogenous regions distal to endothelium. Thus, our data show that binding of fibrin to integrins on endothelial surfaces produces clots that are more resistant to lysis.

Keywords

thrombosisfibrinolysisfibrinendothelial cellsintegrinsconfocal microscopy
Type
Research Article
Information
Microscopy and Microanalysis , Volume 11 , Issue 3 , June 2005 , pp. 268 - 277
Copyright
© 2005 Microscopy Society of America

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