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Apoptotic Platelet Events Are Not Observed in Severe von Willebrand Disease-Type 2B Mutation p.V1316M.

Abstract
Thrombocytopenia and increased platelet clearance observed in von Willebrand disease-type 2B (VWD-2B) may be explained by platelet apoptosis triggered by the constitutive binding of VWF to its receptor, glycoprotein Ib (GPIb). Apoptosis was assessed in platelets from two patients with a severe VWD-2B mutation VWF/p.V1316M and from mice transiently expressing VWF/p.V1316M. We now report that the VWD-2B mutation VWF/p.V1316M which binds spontaneously to its receptor GPIbα does not induce apoptosis. In 2 unrelated patients (P1 and P2) exhibiting different VWF plasma levels (70% and 36%, respectively, compared with normal pooled human plasma given as 100%), inner transmembrane depolarization of mitochondria, characteristic of apoptotic events was undetectable in platelets, whether washed or in whole blood. No or a moderate phosphatidyl serine (PS) exposure as measured by annexin-V staining was observed for P1 and P2, respectively. Expression of pro-apoptotic proteins Bak and Bax, and caspase-3 activity were similar to control platelets. In the VWD-2B mouse model expressing high levels of mVWF/p.V1316M (423%), similar to what is found in inflammatory pathologies, no significant difference was observed between mice expressing mVWF/WT and mVWF/p.V1316M. These results strongly argue against apoptosis as a mechanism for the thrombocytopenia of severe VWD-2B exhibiting the VWF/p.V1316M mutation.
AuthorsEliane Berrou, Alexandre Kauskot, Frédéric Adam, Amélie Harel, Paulette Legendre, Cécile Lavenu Bombled, Chantal Rothschild, Nicolas Prevost, Olivier D Christophe, Peter J Lenting, Cécile V Denis, Jean-Philippe Rosa, Marijke Bryckaert
JournalPloS one (PLoS One) Vol. 10 Issue 12 Pg. e0143896 ( 2015) ISSN: 1932-6203 [Electronic] United States
PMID26645283 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • von Willebrand Factor
Topics
  • Animals
  • Apoptosis (genetics)
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Thrombocytopenia (genetics, pathology)
  • von Willebrand Factor (genetics)

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