TMEM16F-Mediated Platelet Membrane Phospholipid Scrambling Is Critical for Hemostasis and Thrombosis but not Thromboinflammation in Mice-Brief Report

被引：55

作者：

Baig, Ayesha A. ^{[1
,2
]}

Haining, Elizabeth J. ^{[1
,2
]}

Geuss, Eva ^{[3
]}

Beck, Sarah ^{[2
]}

Swieringa, Frauke ^{[4
]}

Wanitchakool, Podchanart ^{[5
]}

Schuhmann, Michael K. ^{[3
]}

Stegner, David ^{[1
,2
]}

Kunzelmann, Karl ^{[5
]}

Kleinschnitz, Christoph ^{[3
,6
]}

Heemskerk, Johan W. M. ^{[4
]}

Braun, Attila ^{[2
]}

Nieswandt, Bernhard ^{[1
,2
]}

机构：

[1] Univ Hosp Wurzburg, Rudolf Virchow Ctr Expt Biomed, Wurzburg, Germany

[2] Univ Hosp Wurzburg, Inst Expt Biomed, Wurzburg, Germany

[3] Univ Hosp Wurzburg, Dept Neurol, Wurzburg, Germany

[4] Maastricht Univ, Dept Biochem, Cardiovasc Res Inst Maastricht CARIM, Maastricht, Netherlands

[5] Univ Regensburg, Dept Physiol, Regensburg, Germany

[6] Univ Duisburg Essen, Med Facil, Neurol Clin, Essen, Germany

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2016年 / 36卷 / 11期

关键词：

blood platelets; fibrin; stroke; thrombin; thrombosis; PHOSPHATIDYLSERINE EXPOSURE; SCOTT-SYNDROME; PROCOAGULANT ACTIVITY; GLYCOPROTEIN-VI; IN-VIVO; PROTEIN; COAGULATION; TMEM16F; ACTIVATION; EXPRESSION;

D O I：

10.1161/ATVBAHA.116.307727

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：2152 / +

页数：18

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