Nitric Oxide Induces Cardiac Protection by Preventing Extracellular Matrix Degradation through the Complex Caveolin-3/EMMPRIN in Cardiac Myocytes.
Autores
Cuadrado Berrocal, Irene; Castejón, Borja; Martín, Ana María; Saura Redondo, Marta; Reventun Torralba, Paula; [et al.]Identificadores
Enlace permanente (URI): http://hdl.handle.net/10017/33764DOI: 10.1371/journal.pone.0162912
PMID: 27649573
ESSN: 1932-6203
Editor
Utpal Sen, University of Louisville, UNITED STATES
Fecha de publicación
2016-09-20Patrocinadores
Ministerio de Economía y Competitividad
Instituto de Salud Carlos III
Cita bibliográfica
PLoS ONE, 2016, v. 11, n. 9, p. e0162912
Palabras clave
Extracellular Matrix
Myocardial Reperfusion Injury
Myocytes, Cardiac
Nitric Oxide
Protective Agents
Proyectos
info:eu-repo/grantAgreement/ISCIII//PI14%2F02022/ES/Inhibición de la degradación de la matriz extracelular como herramienta preventiva frente al ictus isquémico de origen aterosclerótico y su evaluación mediante imagen molecular no invasiva
info:eu-repo/grantAgreement/MINECO//SAF2012-35141/ES/CONTRIBUCIÓN DE LA QUINASA LIGADA A INTEGRINAS (ILK) A LA REGULACIÓN DEL SISTEMA DEL NO Y LA VÍA UB-PROTEASOMA EN LA REMODELACIÓN VASCULAR ASOCIADA A ATEROESCLEROSIS
Tipo de documento
info:eu-repo/semantics/article
Versión
info:eu-repo/semantics/publishedVersion
Derechos
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
(c) Cuadrado et al., 2016
Derechos de acceso
info:eu-repo/semantics/openAccess
Resumen
Inhibition of Extracellular Matrix degradation by nitric oxide (NO) induces cardiac protection against coronary ischemia/reperfusion (IR). Glycosylation of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) stimulates enzymatic activation of matrix metalloproteinases (MMPs) in the heart, although the mechanisms leading to EMMPRIN glycosylation are poorly understood. We sought to determine if NO may induce cardiac protection by preventing glycosylation of EMMPRIN in a mouse model of IR. Here we found that Caveolin-3 binds to low glycosylated EMMPRIN (LG-EMMPRIN) in cardiac cells and in the hearts of healthy mice, whereas IR disrupted the complex in nitric oxide synthase 2 (NOS2) knockout (KO) mice. By contrast, the binding was partially restored when mice were fed with an NO donor (DEA-NO) in the drinking water, showing a significant reduction on infarct size (NOS2KO: 34.6±5 vs NOS2KO+DEA-NO: 20.7±9), in expression of matrix metalloproteinases, and cardiac performance was improved (left ventricular ejection fraction (LVEF). NOS2KO: 31±4 vs NOS2KO+DEA-NO: 46±6). The role of Caveolin-3/EMMPRIN in NO-mediated cardiac protection was further assayed in Caveolin-3 KO mice, showing no significant improvement on infarct size (Caveolin-3 KO: 34.8±3 vs Caveolin-3 KO+DEA-NO:33.7±5), or in the expression of MMPs, suggesting that stabilization of the complex Caveolin-3/LG-EMMPRIN may play a significant role in the cardioprotective effect of NO against IR.
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- FISIOLOG - Artículos [87]