TY - JOUR
T1 - TMEM16F-Mediated Platelet Membrane Phospholipid Scrambling Is Critical for Hemostasis and Thrombosis but not Thromboinflammation in Mice
T2 - Brief Report
AU - Baig, Ayesha A.
AU - Haining, Elizabeth J.
AU - Geuss, Eva
AU - Beck, Sarah
AU - Swieringa, Frauke
AU - Wanitchakool, Podchanart
AU - Schuhmann, Michael K.
AU - Stegner, David
AU - Kunzelmann, Karl
AU - Kleinschnitz, Christoph
AU - Heemskerk, Johan W. M.
AU - Braun, Attila
AU - Nieswandt, Bernhard
PY - 2016/11
Y1 - 2016/11
N2 - Objective-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. Approach and Results-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. Conclusions-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.
AB - Objective-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. Approach and Results-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. Conclusions-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.
KW - blood platelets
KW - fibrin
KW - stroke
KW - thrombin
KW - thrombosis
U2 - 10.1161/ATVBAHA.116.307727
DO - 10.1161/ATVBAHA.116.307727
M3 - Article
SN - 1079-5642
VL - 36
SP - 2152
EP - 2157
JO - Arteriosclerosis Thrombosis and Vascular Biology
JF - Arteriosclerosis Thrombosis and Vascular Biology
IS - 11
ER -