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Thromb Haemost 1995; 74(02): 764-769
DOI: 10.1055/s-0038-1649810
Original Article
Vessel Wall
Schattauer GmbH Stuttgart

Characterization of Endothelial Cell Differential Attachment to Fibrin and Fibrinogen and Its Inhibition by Arg-Gly-Asp-Containing Peptides

Mei-Chi Chang
The Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
,
Bih-Ru Wang
The Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
,
Tur-Fu Huang
The Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
› Author Affiliations
Further Information

Publication History

Received 25 August 1994

Accepted 30 March 1995

Publication Date:
06 July 2018 (online)

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Summary

We investigated the adhesion of human umbilical vein endothelial cells (HUVECs) to fibrin(ogen) molecule of varying structure for identifying sites that mediate cell attachment. Fibrin was prepared either with ancrod which liberates only FPA from fibrinogen, or with thrombin, which liberates both FPA and FPB. Both fibrin preparations equally supported HUVEC attachment. GRGDS, RGD-containing peptides of snake venoms, and monoclonal antibodies against αvβ3 (23C6 and 7E3) inhibited the attachment of HUVECs to fibrin by 65–75%. In contrast, the attachment of HUVECs to fibrinogen was less effective and was almost completely inhibited by both RGD-containing peptides and by antibodies against integrin αvβ3 (85-95% inhibition). The C-terminal dodecapeptide of fibrinogen γ chain (residues 400–411) inhibited minimally the attachment of HUVECs to fibrin. Additionally, the binding of RGD-containing snake venom peptides to HUVECs was both RGD- and divalent-cation-dependent. The IC50s for inhibition of HUVEC attachment to fibrin were 0.09 μM (rhodostomin), 1.54 μM (trigramin) and 1.64 μM (halysin).

These results indicate that fibrin mediated support of cell attachment is independent of the cleavage of FPB from fibrinogen. HUVEC attachment to fibrinogen was almost completely inhibited by RGD-containing peptides and by antibodies against αvβ3. In contrast, the attachment to fibrin was partially resistant to RGD-containing peptides and to the monoclonal antibodies against integrin αvβ3. However, αvβ3 is the major receptor mediating HUVEC attachment to fibrin.

 

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