Connexin 37 limits thrombus propensity by downregulating platelet reactivity
| Autor: | Angelillo-Scherrer Anne, Fontana Pierre, Burnier Laurent, Roth Isabelle, Sugamele Rocco, Brisset Anne, Morel Sandrine, Nolli Séverine, Sutter Esther, Chassot Alexandra, Capron Claude, Borgel Delphine, Saller François, Chanson Marc, Kwak Brenda R, Waltenberger Johannes, Weber Christian, Tokgözoglu Lale |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Bleeding Time Adolescent Megakaryocytes/physiology Connexin Blood Platelets/physiology 030204 cardiovascular system & hematology ddc:616.07 03 medical and health sciences Biotin/analogs & derivatives/pharmacokinetics Mice Young Adult 0302 clinical medicine Bleeding time Platelet Aggregation/physiology Physiology (medical) Down-Regulation/physiology medicine Connexins/genetics/physiology Animals Humans Platelet Thrombus ddc:612 Microinjection 030304 developmental biology ddc:616 0303 health sciences medicine.diagnostic_test business.industry Genetic Predisposition to Disease/genetics Gap junction medicine.disease Mice Mutant Strains Thrombosis/genetics/physiopathology Cell biology Mice Inbred C57BL Gap Junctions/physiology Hemostasis Polymorphism Genetic/physiology Cardiology and Cardiovascular Medicine business Intracellular |
| Zdroj: | Circulation Circulation, Vol. 124, No 8 (2011) pp. 930-9 |
| ISSN: | 0009-7322 |
| DOI: | 10.1161/CIRCULATIONAHA.110.015479 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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