Your browser doesn't support javascript.
loading
The miRNA199a/SIRT1/P300/Yy1/sST2 signaling axis regulates adverse cardiac remodeling following MI.
Asensio-Lopez, Maria Carmen; Sassi, Yassine; Soler, Fernando; Fernandez Del Palacio, Maria Josefa; Pascual-Figal, Domingo; Lax, Antonio.
Afiliación
  • Asensio-Lopez MC; Biomedical Research Institute Virgen de la Arrixaca (IMIB-Arrixaca), University of Murcia, Murcia, Spain.
  • Sassi Y; Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Soler F; Biochemical and Molecular Biology Department, University of Murcia, Murcia, Spain.
  • Fernandez Del Palacio MJ; Veterinary Teaching Hospital, Veterinary Medicine and Surgery Department, University of Murcia, Murcia, Spain.
  • Pascual-Figal D; Cardiology Department, Hospital Virgen de la Arrixaca, IMIB-Arrixaca, University of Murcia, Murcia, Spain. dpascual@um.es.
  • Lax A; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. dpascual@um.es.
Sci Rep ; 11(1): 3915, 2021 02 16.
Article en En | MEDLINE | ID: mdl-33594087
Left ventricular remodeling following myocardial infarction (MI) is related to adverse outcome. It has been shown that an up-regulation of plasma soluble ST2 (sST2) levels are associated with lower pre-discharge left ventricular (LV) ejection fraction, adverse cardiovascular outcomes and mortality outcome after MI. The mechanisms involved in its modulation are unknown and there is not specific treatment capable of lowering plasma sST2 levels in acute-stage HF. We recently identified Yin-yang 1 (Yy1) as a transcription factor related to circulating soluble ST2 isoform (sST2) expression in infarcted myocardium. However, the underlying mechanisms involved in this process have not been thoroughly elucidated. This study aimed to evaluate the pathophysiological implication of miR-199a-5p in cardiac remodeling and the expression of the soluble ST2 isoform. Myocardial infarction (MI) was induced by permanent ligation of the left anterior coronary artery in C57BL6/J mice that randomly received antimiR199a therapy, antimiR-Ctrl or saline. A model of biomechanical stretching was also used to characterize the underlying mechanisms involved in the activation of Yy1/sST2 axis. Our results show that the significant upregulation of miR-199a-5p after myocardial infarction increases pathological cardiac hypertrophy by upregulating circulating soluble sST2 levels. AntimiR199a therapy up-regulates Sirt1 and inactivates the co-activator P300 protein, thus leading to Yy1 inhibition which decreases both expression and release of circulating sST2 by cardiomyocytes after myocardial infarction. Pharmacological inhibition of miR-199a rescues cardiac hypertrophy and heart failure in mice, offering a potential therapeutic approach for cardiac failure.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hipertrofia Ventricular Izquierda / Remodelación Ventricular / MicroARNs / Proteína 1 Similar al Receptor de Interleucina-1 / Infarto del Miocardio Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hipertrofia Ventricular Izquierda / Remodelación Ventricular / MicroARNs / Proteína 1 Similar al Receptor de Interleucina-1 / Infarto del Miocardio Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido