Abstract
Platelet activation and aggregation at sites of vascular injury is essential to prevent excessive blood loss, but may also trigger life-threatening cardio- and cerebrovascular disease conditions. In vitro studies have significantly contributed to the current knowledge of central signaling pathways underlying platelet activation. However, in vitro experimental conditions cannot reproduce the complex environment with specific hemodynamic conditions in which interactions between platelets, other blood cell types, and the vessel wall take place. Intravital microscopy studies in experimental animal models, in particular mice, have advanced our understanding of the spatiotemporal characteristics and molecular pathways controlling thrombus formation in vivo. State-of-the-art imaging modalities together with essential tools allowing manipulations of the mouse genome have enabled us to explore new avenues toward the development of novel effective, yet safe antiplatelet drugs. This chapter summarizes widely used techniques to study in vivo thrombus formation and highlights data obtained in mouse models on the role of distinct platelet surface receptors, soluble platelet agonists, and the intrinsic coagulation cascade in thrombosis. Based on experimental evidence, the suitability of several platelet receptors and coagulation factors as novel targets for antithrombotic therapy is discussed.
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Acknowledgments
Prof. Dr. Bernhard Nieswandt holds the Chair of Experimental Biomedicine at the University Hospital and the Rudolf Virchow Center, University of Würzburg, Germany. This work was supported by the Deutsche Forschungsgemeinschaft (SFB 688) and the Rudolf Virchow Center. Dr. Deya Cherpokova was supported by a grant of the German Excellence Initiative to the Graduate School of Life Sciences, University of Würzburg.
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Cherpokova, D., Nieswandt, B. (2017). Mouse Models of Thrombosis. In: Gresele, P., Kleiman, N., Lopez, J., Page, C. (eds) Platelets in Thrombotic and Non-Thrombotic Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-47462-5_46
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