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10.1161/ATVBAHA.116.307660

http://scihub22266oqcxt.onion/10.1161/ATVBAHA.116.307660
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suck abstract from ncbi


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pmid27444201
      Arterioscler+Thromb+Vasc+Biol 2016 ; 36 (9 ): 1829-37
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  • Endothelial Cell-Derived von Willebrand Factor Is the Major Determinant That Mediates von Willebrand Factor-Dependent Acute Ischemic Stroke by Promoting Postischemic Thrombo-Inflammation #MMPMID27444201
  • Dhanesha N ; Prakash P ; Doddapattar P ; Khanna I ; Pollpeter MJ ; Nayak MK ; Staber JM ; Chauhan AK
  • Arterioscler Thromb Vasc Biol 2016[Sep]; 36 (9 ): 1829-37 PMID27444201 show ga
  • OBJECTIVE: von Willebrand factor (VWF), which is synthesized in endothelial cells and megakaryocytes, is known to worsen stroke outcome. In vitro studies suggest that platelet-derived VWF (Plt-VWF) is biochemically different from the endothelial cell-derived VWF (EC-VWF). However, little is known about relative contribution of different pools of VWF in stroke. APPROACH AND RESULTS: Using bone marrow transplantation, we generated chimeric Plt-VWF mice, Plt-VWF mice that lack ADAMTS13 in platelets and plasma (Plt-VWF/Adamts13(-/-)), and EC-VWF mice to determine relative contribution of different pools of VWF in stroke. In brain ischemia/reperfusion injury model, we found that infarct size and postischemic intracerebral thrombo-inflammation (fibrin(ogen) deposition, neutrophil infiltration, interleukin-1?, and tumor necrosis factor-? levels) within lesions were comparable between EC-VWF and wild-type mice. Infarct size and postischemic thrombo-inflammation were comparable between Plt-VWF and Plt-VWF/Adamts13(-/-) mice, but decreased compared with EC-VWF and wild-type mice (P<0.05) and increased compared with Vwf(-/-) mice (P<0.05). Susceptibility to FeCl3 injury-induced carotid artery thrombosis was comparable between wild-type and EC-VWF mice, whereas Plt-VWF and Plt-VWF/Adamts13(-/-) mice exhibited defective thrombosis. Although most of the injured vessels did not occlude, slope over time showed that thrombus growth rate was increased in both Plt-VWF and Plt-VWF/Adamts13(-/-) mice compared with Vwf(-/-) mice (P<0.05), but decreased compared with wild-type or EC-VWF mice. CONCLUSIONS: Plt-VWF, either in presence or absence of ADAMTS13, partially contributes to VWF-dependent injury and postischemic thrombo-inflammation after stroke. EC-VWF is the major determinant that mediates VWF-dependent ischemic stroke by promoting postischemic thrombo-inflammation.
  • |ADAMTS13 Protein/deficiency/genetics [MESH]
  • |Animals [MESH]
  • |Blood Platelets/metabolism [MESH]
  • |Bone Marrow Transplantation [MESH]
  • |Carotid Artery Diseases/chemically induced/genetics/*metabolism/pathology [MESH]
  • |Chlorides [MESH]
  • |Disease Models, Animal [MESH]
  • |Endothelial Cells/*metabolism [MESH]
  • |Ferric Compounds [MESH]
  • |Genetic Predisposition to Disease [MESH]
  • |Infarction, Middle Cerebral Artery/genetics/*metabolism/pathology [MESH]
  • |Inflammation Mediators/metabolism [MESH]
  • |Inflammation/genetics/*metabolism/pathology [MESH]
  • |Lasers [MESH]
  • |Male [MESH]
  • |Mesenteric Vascular Occlusion/genetics/*metabolism/pathology [MESH]
  • |Mice, Inbred C57BL [MESH]
  • |Mice, Knockout [MESH]
  • |Neutrophil Infiltration [MESH]
  • |Phenotype [MESH]
  • |Platelet Transfusion [MESH]
  • |Reperfusion Injury/genetics/*metabolism/pathology [MESH]
  • |Signal Transduction [MESH]
  • |Thrombosis/chemically induced/genetics/*metabolism/pathology [MESH]
  • |Time Factors [MESH]


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