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K. Suzuki-Inoue, Gemma Fuller, Ángel García, J. Eble, S. Pöhlmann, O. Inoue, T. Gartner, S. Hughan, Andrew Pearce, G. Laing, R. Theakston, E. Schweighoffer, N. Zitzmann, T. Morita, V. Tybulewicz, Y. Ozaki, S. Watson (2006)
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Supplemental Figure III. Generation of Gp6 -/-mice
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Combined In Vivo Depletion of Glycoprotein VI and C-Type Lectin-Like Receptor 2 Severely Compromises Hemostasis and Abrogates Arterial Thrombosis in Mice Markus Bender, Frauke May, Viola Lorenz, Ina Thielmann, Ina Hagedorn, Brenda A. Finney, Timo Vögtle, Katharina Remer, Attila Braun, Michael Bösl, Steve P. Watson, Bernhard Nieswandt Objective—Platelet inhibition is a major strategy to prevent acute ischemic cardiovascular and cerebrovascular events, which may, however, be associated with an increased bleeding risk. The (hem)immunoreceptor tyrosine activation motif– bearing platelet receptors, glycoprotein VI (GPVI) and C-type lectin-like receptor 2 (CLEC-2), might be promising antithrombotic targets because they can be depleted from circulating platelets by antibody treatment, leading to sustained antithrombotic protection, but only moderately increased bleeding times in mice. Approach and Results—We investigated whether both (hem)immunoreceptor tyrosine activation motif–bearing receptors can be targeted simultaneously and what the in vivo consequences of such a combined therapeutic GPVI/CLEC-2 deficiency are. We demonstrate that isolated targeting of either GPVI or CLEC-2 in vivo does not affect expression or function of the respective other receptor. Moreover, simultaneous treatment with both antibodies resulted in the sustained loss of both GPVI and CLEC-2, while leaving other activation pathways intact. However, GPVI/CLEC-2–depleted mice displayed a dramatic hemostatic defect
Arteriosclerosis, Thrombosis, and Vascular Biology – Wolters Kluwer Health
Published: May 1, 2013
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