Murine cadherin‐6 mediates thrombosis in vivo in a platelet‐independent manner
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/rth2.12458 |
| _version_ | 1797714395958083584 |
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| author | Emma G. Bouck Maria de laFuente Elizabeth R. Zunica Wei Li Michele M. Mumaw Marvin T. Nieman |
| author_facet | Emma G. Bouck Maria de laFuente Elizabeth R. Zunica Wei Li Michele M. Mumaw Marvin T. Nieman |
| author_sort | Emma G. Bouck |
| collection | DOAJ |
| description | 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, aggregometry, and flow cytometry. Results 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. 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. |
| first_indexed | 2024-03-12T07:51:16Z |
| format | Article |
| id | doaj.art-e1858e91bc914b1f96ae3f1bec6abab5 |
| institution | Directory Open Access Journal |
| issn | 2475-0379 |
| language | English |
| last_indexed | 2024-03-12T07:51:16Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj.art-e1858e91bc914b1f96ae3f1bec6abab52023-09-02T20:36:17ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792021-01-015112513110.1002/rth2.12458Murine cadherin‐6 mediates thrombosis in vivo in a platelet‐independent mannerEmma G. Bouck0Maria de laFuente1Elizabeth R. Zunica2Wei Li3Michele M. Mumaw4Marvin T. Nieman5Department of Pharmacology Case Western Reserve University Cleveland OH USADepartment of Pharmacology Case Western Reserve University Cleveland OH USADepartment of Pharmacology Case Western Reserve University Cleveland OH USADeparmtent of Biomedical Sciences Marshall University Joan C. Edwards School of Medicine Huntington WV USADepartment of Pharmacology Case Western Reserve University Cleveland OH USADepartment of Pharmacology Case Western Reserve University Cleveland OH USAAbstract 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, aggregometry, and flow cytometry. Results 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. 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.https://doi.org/10.1002/rth2.12458arterial thrombosiscadherin‐6mouse modelplatelet adhesion |
| spellingShingle | Emma G. Bouck Maria de laFuente Elizabeth R. Zunica Wei Li Michele M. Mumaw Marvin T. Nieman Murine cadherin‐6 mediates thrombosis in vivo in a platelet‐independent manner Research and Practice in Thrombosis and Haemostasis arterial thrombosis cadherin‐6 mouse model platelet adhesion |
| title | Murine cadherin‐6 mediates thrombosis in vivo in a platelet‐independent manner |
| title_full | Murine cadherin‐6 mediates thrombosis in vivo in a platelet‐independent manner |
| title_fullStr | Murine cadherin‐6 mediates thrombosis in vivo in a platelet‐independent manner |
| title_full_unstemmed | Murine cadherin‐6 mediates thrombosis in vivo in a platelet‐independent manner |
| title_short | Murine cadherin‐6 mediates thrombosis in vivo in a platelet‐independent manner |
| title_sort | murine cadherin 6 mediates thrombosis in vivo in a platelet independent manner |
| topic | arterial thrombosis cadherin‐6 mouse model platelet adhesion |
| url | https://doi.org/10.1002/rth2.12458 |
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