Platelet-derived VWF is not essential for normal thrombosis and hemostasis but fosters ischemic stroke injury in mice

Verhenne, Sebastien; Denorme, Frederik; Libbrecht, Sarah; Vandenbulcke, Aline; Pareyn, Inge; Deckmyn, Hans; Lambrecht, Antoon; Nieswandt, Bernhard; Kleinschnitz, Christoph; Vanhoorelbeke, Karen; Meyer, Simon F. De

doi:10.1182/blood-2015-03-632901

Cited by 66 publications

(59 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…11 VWF is synthesized by ECs and megakaryocytes and is stored as ultra large VWF multimers or high molecular weight multimers in the endothelial Weibel-Palade bodies or the platelet α-granules, respectively. 12 Plasma VWF was thought to be derived from the secretion of ECs and platelets and could be enhanced by secretagogues. 12 Although numerous studies have revealed the roles of VWF on hemostasis and coagulation, the differences between the endothelial VWF and the platelet VWF in thrombotic and thrombosis-related diseases are unclear.…”

Section: Von Willebrand Factormentioning

confidence: 99%

“…12 Plasma VWF was thought to be derived from the secretion of ECs and platelets and could be enhanced by secretagogues. 12 Although numerous studies have revealed the roles of VWF on hemostasis and coagulation, the differences between the endothelial VWF and the platelet VWF in thrombotic and thrombosis-related diseases are unclear. Dhanesha et al 13 examined the roles of endothelial and platelet VWF in thrombosis in vivo.…”

Section: Von Willebrand Factormentioning

confidence: 99%

See 1 more Smart Citation

Thrombotic Regulation From the Endothelial Cell Perspectives

Wang

Hao

Leeper

et al. 2018

ATVB

136

View full text Add to dashboard Cite

Section: Von Willebrand Factormentioning

confidence: 99%

Section: Von Willebrand Factormentioning

confidence: 99%

Thrombotic Regulation From the Endothelial Cell Perspectives

Wang

Hao

Leeper

et al. 2018

ATVB

136

View full text Add to dashboard Cite

“…25 Of note, this study did not quantify the overall local levels of VWF in the infarcted and surrounding region following stroke. Similar to the Verhenne et al study, we found that chimeric Plt-VWF mice exhibited significantly bigger infarcts compared to VWF-KO mice.…”

Section: Discussionmentioning

confidence: 94%

Endothelial Cell–Derived von Willebrand Factor Is the Major Determinant That Mediates von Willebrand Factor–Dependent Acute Ischemic Stroke by Promoting Postischemic Thrombo-Inflammation

Dhanesha

Prakash

Doddapattar

et al. 2016

ATVB

View full text Add to dashboard Cite

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 is biochemically different from the endothelial cell-derived 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 platelet derived-VWF mice (Plt-VWF), platelet derived-VWF mice that lack ADAMTS13 in platelets and plasma (Plt-VWF/Adamts13−/−), and endothelial cell derived-VWF mice (EC-VWF) to determine relative contribution of different pools of VWF in stroke. In brain ischemia/reperfusion injury model, we found that infarct size, post-ischemic intracerebral thrombo-inflammation (fibrin(ogen) deposition, neutrophil infiltration, IL-1β and TNF-α levels) within lesions were comparable between EC-VWF and WT mice. Infarct size and post-ischemic thrombo-inflammation were comparable between Plt-VWF and Plt-VWF/Adamts13−/− mice, but decreased compared to EC-VWF and/or WT mice (P<0.05) and increased compared to Vwf −/− mice (P<0.05). Susceptibility to FeCl3 injury-induced carotid artery thrombosis was comparable between WT 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 to Vwf −/− mice (P<0.05), but decreased compared to WT or EC-VWF mice. Conclusions Platelet-derived VWF, either in presence or absence of ADAMTS13, partially contributes to VWF-dependent injury and post-ischemic thrombo-inflammation following stroke. Endothelial cell-derived VWF is the major determinant that mediates VWF-dependent ischemic stroke by promoting post-ischemic thrombo-inflammation.

show abstract

“…1 They created mice with either endothelial VWF or platelet-derived VWF and examined each phenotype for bleeding and thrombosis. Their intriguing findings were that mice lacking platelet-derived VWF, but with adequate endothelial VWF stores, demonstrated normal hemostasis in a tail bleeding model and normal carotid artery thrombosis.…”

mentioning

confidence: 99%

“…Verhenne et al use an anti-GPIba antibody in their stroke model and show a corresponding reduction in the effect of platelet-derived VWF, as would be expected if GPIb is the major driver in this interaction. 1 Platelets themselves have been implicated in stroke, with aspirin playing a key role in treatment and prevention. 6 The paradigm in which antiplatelet agents are used, however, has generally been that of preventing platelet aggregation rather than preventing release of prothrombotic VWF.…”

mentioning

confidence: 99%