Connexin 37 limits thrombus propensity by downregulating platelet reactivity.

Détails

ID Serval
serval:BIB_2BE789B05435
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Connexin 37 limits thrombus propensity by downregulating platelet reactivity.
Périodique
Circulation
Auteur(s)
Angelillo-Scherrer A., Fontana P., Burnier L., Roth I., Sugamele R., Brisset A., Morel S., Nolli S., Sutter E., Chassot A., Capron C., Borgel D., Saller F., Chanson M., Kwak B.R.
ISSN
1524-4539 (Electronic)
ISSN-L
0009-7322
Statut éditorial
Publié
Date de publication
2011
Volume
124
Numéro
8
Pages
930-939
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
Background- Formation of platelet plug initiates hemostasis after vascular injury and triggers thrombosis in ischemic disease. However, the mechanisms leading to the formation of a stable thrombus are poorly understood. Connexins comprise a family of proteins that form gap junctions enabling intercellular coordination of tissue activity, a process termed gap junctional intercellular communication. Methods and Results- In the present study, we show that megakaryocytes and platelets express connexin 37 (Cx37). Deletion of the Cx37 gene in mice shortens bleeding time and increases thrombus propensity. Aggregation is increased in murine Cx37(-/-) platelets or in murine Cx37(+/+) and human platelets treated with gap junction blockers. Intracellular microinjection of neurobiotin, a Cx37-permeant tracer, revealed gap junctional intercellular communication in platelet aggregates, which was impaired in Cx37(-/-) platelets and in human platelets exposed to gap junction blockers. Finally, healthy subjects homozygous for Cx37-1019C, a prognostic marker for atherosclerosis, display increased platelet responses compared with subjects carrying the Cx37-1019T allele. Expression of these polymorphic channels in communication-deficient cells revealed a decreased permeability of Cx37-1019C channels for neurobiotin. Conclusions- We propose that the establishment of gap junctional communication between Cx37-expressing platelets provides a mechanism to limit thrombus propensity. To our knowledge, these data provide the first evidence incriminating gap junctions in the pathogenesis of thrombosis.
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/09/2011 10:51
Dernière modification de la notice
08/05/2019 16:22
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