HomeStrokeVol. 42, No. 3Letter by De Meyer et al Regarding Article “High von Willebrand Factor Levels Increase the Risk of Stroke: The Rotterdam Study” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessLetterPDF/EPUBLetter by De Meyer et al Regarding Article “High von Willebrand Factor Levels Increase the Risk of Stroke: The Rotterdam Study” Simon F. De Meyer, Guido Stoll and Christoph Kleinschnitz Simon F. De MeyerSimon F. De Meyer Search for more papers by this author , Guido StollGuido Stoll Search for more papers by this author and Christoph KleinschnitzChristoph Kleinschnitz Search for more papers by this author Originally published3 Feb 2011https://doi.org/10.1161/STROKEAHA.110.604777Stroke. 2011;42:e41Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 To the Editor:With great interest, we read the article by Wieberdink et al, published in the October 2010 issue of Stroke.1 In this relevant study (as part of the Rotterdam Study), the authors investigated the association between plasma levels of von Willebrand factor (VWF) and the overall risk of stroke. To this end, a large population-based cohort of 6250 participants (age ≥55 years) who were free of stroke at baseline was followed for 5 years. Interestingly, the authors found that the risk of stroke increased with increasing VWF levels, independent from conventional cardiovascular risk factors and ABO blood group status; this clearly indicates an association between the amount of circulating VWF and the risk of stroke in this elderly population.While not discussed by the authors, their findings further confirm a critical role for VWF in stroke development, as shown in several recent studies of experimental stroke. Indeed, we recently demonstrated that VWF-deficient mice are protected from ischemic brain injury, evidenced by a dramatic reduction of infarct volume (approximately 60% of the infarct volumes in wild-type controls) and better functional outcome.2 Similar results were obtained in an independent study by Zhao et al.3 Reconstitution of plasma VWF in VWF-deficient mice by hydrodynamic gene transfer fully restored the susceptibility to cerebral ischemia.2 Furthermore, in a study aimed at the identification of crucial VWF interactions in stroke, we demonstrated that in VWF-deficient mice reconstituted with VWF mutants defective in binding to collagen or platelet glycoprotein (GP) Ibα, protection against stroke was sustained; however, VWF lacking the GPIIb/IIIa binding site restored full susceptibility to stroke similar to normal VWF.4 Thus, binding of VWF to both collagen and GPIb (but not to GPIIb/IIIa) are mandatory steps in stroke development. In addition, the central role of VWF in stroke development has recently been underlined by observations that VWF-cleaving protease a disintegrin and metalloprotease with thrombospondin type 1 repeats, 13 (referred to simply as ADAMTS13), which decreases the thrombogenicity of VWF by cleaving ultralarge VWF multimers into smaller ones, also plays a protective role in cerebral ischemia.3,5Taken together, we are excited to see that the findings of Wieberdink et al in humans nicely fit into the general concept of VWF as an important mediator of experimental stroke. The growing amount of data all point toward VWF as an attractive target for stroke prevention and treatment.Simon F. De Meyer, PhDGuido Stoll, MDChristoph Kleinschnitz, MD Immune Disease Institute Program in Cellular and Molecular Medicine, Children's Hospital Boston, and Department of Pathology Harvard Medical School Boston, MA Department of Neurology University of Wuerzburg Wuerzburg, GermanyFootnotesStroke welcomes Letters to the Editor and will publish them, if suitable, as space permits. Letters must reference a Stroke published-ahead-of-print article or an article printed within the past 3 weeks. The maximum length is 750 words including no more than 5 references and 3 authors. Please submit letters typed double-spaced. Letters may be shortened or edited. Include a completed copyright transfer agreement form (available online at http://stroke.ahajournals.org and http://submit-stroke.ahajournals.org).
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