Ivabradine-Stimulated Microvesicle Release Induces Cardiac Protection against Acute Myocardial Infarction.
dc.contributor.author | Ramírez Carracedo, Rafael | |
dc.contributor.author | Tesoro Santos, Laura | |
dc.contributor.author | Hernández, Ignacio | |
dc.contributor.author | Díez Mata, Javier | |
dc.contributor.author | Botana, Laura | |
dc.contributor.author | Saura, Marta | |
dc.contributor.author | Sanmartin, Marcelo | |
dc.contributor.author | Zamorano, José Luis | |
dc.contributor.author | Zaragoza Sánchez, Carlos | |
dc.date.accessioned | 2020-09-21T08:47:08Z | |
dc.date.available | 2020-09-21T08:47:08Z | |
dc.date.issued | 2020 | |
dc.description.abstract | Ivabradine 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 microvesicles. | spa |
dc.description.extent | 1810 KB | spa |
dc.identifier.doi | 10.3390/ijms21186566 | spa |
dc.identifier.issn | 1422-0067 | spa |
dc.identifier.uri | http://hdl.handle.net/10641/1980 | |
dc.language.iso | eng | spa |
dc.publisher | International Journal of Molecular Sciences | spa |
dc.relation.publisherversion | https://www.mdpi.com/1422-0067/21/18/6566 | spa |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.accessRights | open access | spa |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | Acute myocardial infarction | spa |
dc.subject | Ischemia reperfusion | spa |
dc.subject | Microvesicles | spa |
dc.subject | Ivabradine | spa |
dc.subject | EMMPRIN | spa |
dc.title | Ivabradine-Stimulated Microvesicle Release Induces Cardiac Protection against Acute Myocardial Infarction. | spa |
dc.type | journal article | spa |
dc.type.hasVersion | AM | spa |
dspace.entity.type | Publication | |
relation.isAuthorOfPublication | a1854c1f-1c01-4cee-a866-fd372311dc18 | |
relation.isAuthorOfPublication | f739a89c-f1cb-4d99-a0e8-560a8b063182 | |
relation.isAuthorOfPublication | d8b48195-2b61-490d-8a8f-69b4079a6847 | |
relation.isAuthorOfPublication.latestForDiscovery | a1854c1f-1c01-4cee-a866-fd372311dc18 |
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