Cadherin 6 has a functional role in platelet aggregation and thrombus formation.

Eimear Dunne, Christopher M. Spring, Adili Reheman, Wuxun Jin, Michael C. Berndt, Debra K. Newman, Peter J. Newman, Heyu Ni, Dermot Kenny

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32 Citations (Scopus)

Abstract

Thrombosis occurs at sites of vascular injury when platelets adhere to subendothelial matrix proteins and to each other. Platelets express many surface receptor proteins, the function of several of these remains poorly characterized. Cadherin 6 is expressed on the platelet surface and contains an arginine-glycine-aspartic acid motif, suggesting that it might have a supportive role in thrombus formation. The aim of this study was to characterize the role of cadherin 6 in platelet function. Platelet aggregation was inhibited by both antibodies and exogenous soluble cadherin 6. Platelet adhesion to immobilized cadherin 6 was inhibited by arginine-glycine-aspartic acid-serine tetrapeptides. Antibodies to α(IIb)β(3) inhibited platelet adhesion to cadherin 6. Because platelet aggregation occurs in fibrinogen and von Willebrand factor double-deficient mice, we investigated whether cadherin 6 is an alternative ligand for the integrin α(IIb)β(3). Platelet aggregation in fibrinogen and von Willebrand factor double-deficient mice was significantly inhibited by an antibody to cadherin 6. In flow-based assays, inhibition of cadherin 6 caused a marked reduction in thrombus formation in both human and mouse blood. This study demonstrates the role of cadherin 6 as a novel ligand for α(IIb)β(3) and highlights its function in thrombus formation.

Original languageEnglish
Pages (from-to)1724-1731
Number of pages8
JournalArteriosclerosis, Thrombosis and Vascular Biology
Volume32
Issue number7
DOIs
Publication statusPublished - Jul 2012
Externally publishedYes

Cite this

Dunne, E., Spring, C. M., Reheman, A., Jin, W., Berndt, M. C., Newman, D. K., Newman, P. J., Ni, H., & Kenny, D. (2012). Cadherin 6 has a functional role in platelet aggregation and thrombus formation. Arteriosclerosis, Thrombosis and Vascular Biology, 32(7), 1724-1731. https://doi.org/10.1161/ATVBAHA.112.250464