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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Arterioscler+Thromb+Vasc+Biol
2016 ; 36
(9
): 1829-37
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English Wikipedia
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.