Baig Ayesha A, Haining Elizabeth J, Geuss Eva, Beck Sarah, Swieringa Frauke, Wanitchakool Podchanart, Schuhmann Michael K, Stegner David, Kunzelmann Karl, Kleinschnitz Christoph, Heemskerk Johan W M, Braun Attila, Nieswandt Bernhard
From the Rudolf Virchow Center for Experimental Biomedicine (A.A.B., E.J.H., D.S., B.N.), Institute of Experimental Biomedicine (A.A.B., E.J.H., S.B., D.S., A.B., B.N.), and Department of Neurology (E.G., M.K.S., C.K.), University Hospital of Würzburg and University of Würzburg, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (F.S., J.W.M.H.); Department of Physiology, University of Regensburg, Germany (P.W., K.K.); and Clinic for Neurology, University of Duisburg-Essen Medical Facility, Essen, Germany (C.K.).
Arterioscler Thromb Vasc Biol. 2016 Nov;36(11):2152-2157. doi: 10.1161/ATVBAHA.116.307727. Epub 2016 Sep 15.
It is known that both platelets and coagulation strongly influence infarct progression after ischemic stroke, but the mechanisms and their interplay are unknown. Our aim was to assess the contribution of the procoagulant platelet surface, and thus platelet-driven thrombin generation, to the progression of thromboinflammation in the ischemic brain.
We present the characterization of a novel platelet and megakaryocyte-specific TMEM16F (anoctamin 6) knockout mouse. Reflecting Scott syndrome, platelets from the knockout mouse had a significant reduction in procoagulant characteristics that altered thrombin and fibrin generation kinetics. In addition, knockout mice showed significant defects in hemostasis and arterial thrombus formation. However, infarct volumes in a model of ischemic stroke were comparable with wild-type mice.
Platelet TMEM16F activity contributes significantly to hemostasis and thrombosis but not cerebral thromboinflammation. These results highlight another key difference between the roles of platelets and coagulation in these processes.
已知血小板和凝血均对缺血性卒中后的梗死进展有强烈影响，但机制及其相互作用尚不清楚。我们的目的是评估促凝血小板表面以及由此产生的血小板驱动的凝血酶生成对缺血性脑内血栓炎症进展的作用。
我们展示了一种新型血小板和巨核细胞特异性跨膜蛋白16F（anoctamin 6，TMEM16F）基因敲除小鼠的特征。该基因敲除小鼠的血小板反映了斯科特综合征，其促凝特性显著降低，改变了凝血酶和纤维蛋白生成动力学。此外，基因敲除小鼠在止血和动脉血栓形成方面表现出明显缺陷。然而，在缺血性卒中模型中，梗死体积与野生型小鼠相当。
血小板TMEM16F活性对止血和血栓形成有显著贡献，但对脑内血栓炎症无影响。这些结果突出了血小板和凝血在这些过程中的作用的另一个关键差异。
