Murine cadherin‐6 mediates thrombosis in vivo in a platelet‐independent manner

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. We aimed to further characterize the importance of cadherin‐6 in thrombosis in vivo. 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, aggregometry, and flow cytometry. Human platelet expression of cadherin‐6 was confirmed at ~3000 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, platelet aggregation, or platelet activation in wild‐type versus Cdh6−/− mice. 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.