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bioRxiv · 10.1101/2020.04.20.051045

Cadherin-6 mediates thrombosis in vivo

Bouck, E. G.·de la Fuente, M.·Zunica, E. R.·Li, W.·Mumaw, M. M.·Nieman, M. T.
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Abstract

Background Platelet adhesion is the critical process mediating stable thrombus formation. Previous reports of cadherin-6 on human platelets have demonstrated its role in platelet aggregation and thrombus formation.Objectives We aimed to further characterize the importance of cadherin-6 in thrombosis in vivo.Methods Cadherin-6 platelet expression was evaluated by western blotting, flow cytometry and immunoprecipitation. Thrombosis was evaluated using the FeCl3 and Rose Bengal carotid artery models in C57Bl6 mice treated with anti-cadherin-6 or IgG and wild-type or Cdh6-/- mice. Platelet function was compared in wild type and Cdh6-/- mice using tail-clip assays and aggregometry.Results Human platelet expression of cadherin-6 was confirmed at ~3,000 copies per platelet. Cdh6-/- mice or those treated with anti-Cadherin-6 antibody showed an increased time to occlusion in both thrombosis models. Cadherin-6 was not expressed on mouse platelets, and there were no differences in tail bleeding times or platelet aggregation in wild-type versus Cdh6-/- mice.Conclusions Cadherin-6 plays an essential role in thrombosis in vivo. However, cadherin-6 is not expressed on murine platelets. These data are in contrast to human platelets, which express a functional cadherin-6/catenin complex. The essential, platelet-independent role for cadherin-6 in hemostasis may allow it to be an effective and safe therapeutic target.EssentialsCadherin-6 function in thrombus formation was investigated in vivo using two murine models of thrombosis.Blocking or deleting cadherin-6 significantly delayed time to occlusionHuman platelets express cadherin-6, but murine platelets do not.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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Bouck, E. G., de la Fuente, M., Zunica, E. R., Li, W., Mumaw, M. M., Nieman, M. T.. 2020-04-21. Cadherin-6 mediates thrombosis in vivo. https://doi.org/10.1101/2020.04.20.051045

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