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dc.contributor.authorRamírez Carracedo, Rafael
dc.contributor.authorTesoro, Laura
dc.contributor.authorHernández, Ignacio
dc.contributor.authorDíez Mata, Javier
dc.contributor.authorBotana, Laura
dc.contributor.authorSaura, Marta
dc.contributor.authorSanmartin, Marcelo
dc.contributor.authorZamorano, José Luis
dc.contributor.authorZaragoza Sánchez, Carlos
dc.description.abstractIvabradine can reduce heart rate through inhibition of the current I(f ) by still unexplored mechanisms. In a porcine model of ischemia reperfusion (IR), we found that treatment with 0.3 mg/kg Ivabradine increased plasma release of microvesicles (MVs) over Placebo, as detected by flow cytometry of plasma isolated from pigs 7 days after IR, in which a tenfold increase of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) containing (both high and low-glycosylated) MVs, was detected in response to Ivabradine. The source of MVs was investigated, finding a 37% decrease of CD31+ endothelial cell derived MVs, while CD41+ platelet MVs remained unchanged. By contrast, Ivabradine induced the release of HCN4+ (mostly cardiac) MVs. While no differences respect to EMMPRIN as a cargo component were found in endothelial and platelet derived MVs, Ivabradine induced a significant release of EMMPRIN+/HCN4+ MVs by day 7 after IR. To test the role of EMMPRIN+ cardiacMVs (EMCMV), H9c2 cellmonolayers were incubated for 24 h with 107 EMCMVs, reducing apoptosis, and increasing 2 times cell proliferation and 1.5 times cell migration. The in vivo contribution of Ivabradine-induced plasma MVs was also tested, in which 108 MVs isolated from the plasma of pigs treated with Ivabradine or Placebo 7 days after IR, were injected in pigs under IR, finding a significant cardiac protection by increasing left ventricle ejection fraction and a significant reduction of the necrotic area. In conclusion ivabradine induces cardiac protection by increasing at least the release of EMMPRIN containing cardiac
dc.publisherInternational Journal of Molecular Sciencesspa
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 España*
dc.subjectAcute myocardial infarctionspa
dc.subjectIschemia reperfusionspa
dc.titleIvabradine-Stimulated Microvesicle Release Induces Cardiac Protection against Acute Myocardial
dc.description.extent1810 KBspa

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