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TMEM16F-Mediated Platelet Membrane Phospholipid Scrambling Is Critical for Hemostasis and Thrombosis but not Thromboinflammation in Mice
- Source :
- Arteriosclerosis Thrombosis and Vascular Biology, 36(11), 2152-2157. LIPPINCOTT WILLIAMS & WILKINS
- Publication Year :
- 2016
-
Abstract
- 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.
- Subjects :
- Carotid Artery Diseases
0301 basic medicine
blood platelets
Medizin
Anoctamins
Phosphatidylserines
030204 cardiovascular system & hematology
Pharmacology
Fibrin
03 medical and health sciences
0302 clinical medicine
Thrombin
Phospholipid scrambling
Scott syndrome
medicine
Animals
Platelet
Platelet activation
fibrin
Phospholipid Transfer Proteins
Blood Coagulation
thrombosis
Mice, Knockout
Hemostasis
biology
Chemistry
Infarction, Middle Cerebral Artery
Platelet Activation
medicine.disease
stroke
thrombin
Mice, Inbred C57BL
Disease Models, Animal
Kinetics
030104 developmental biology
Coagulation
Immunology
biology.protein
Encephalitis
Cardiology and Cardiovascular Medicine
Megakaryocytes
Signal Transduction
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 10795642
- Volume :
- 36
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Arteriosclerosis Thrombosis and Vascular Biology
- Accession number :
- edsair.doi.dedup.....fc53be583f3f251689677476524da425