miR-133a Enhances the Protective Capacity of Cardiac Progenitors Cells after Myocardial Infarction

Autores de IIS La Fe

• Inmaculada Cerrada Serra

  Autor

• Antonio Diez Juan

  Autor

• Iñigo Valiente Alandi

  Autor

• Amparo Ruiz Sauri

  Autor

• 

  Pilar Sepúlveda Sanchis

  Autor

• Ana M Bernad Felices

  Autor

Participantes ajenos a IIS La Fe

• Izarra A
• Moscoso I
• Levent E
• Cañón S
• Blanca V
• Núñez-Gil IJ
• Tiburcy M
• Zimmermann WH

Grupos

• Regeneración y Trasplante Cardíaco

  

  Leader

  Pilar Sepúlveda Sanchis

Abstract

miR-133a and miR-1 are known as muscle-specific microRNAs that are involved in cardiac development and pathophysiology. We have shown that both miR-1 and miR-133a are early and progressively upregulated during in vitro cardiac differentiation of adult cardiac progenitor cells (CPCs), but only miR-133a expression was enhanced under in vitro oxidative stress. miR-1 was demonstrated to favor differentiation of CPCs, whereas miR-133a overexpression protected CPCs against cell death, targeting, among others, the proapoptotic genes Bim and Bmf. miR-133a-CPCs clearly improved cardiac function in a rat myocardial infarction model by reducing fibrosis and hypertrophy and increasing vascularization and cardiomyocyte proliferation. The beneficial effects of miR-133a-CPCs seem to correlate with the upregulated expression of several relevant paracrine factors and the plausible cooperative secretion of miR-133a via exosomal transport. Finally, an in vitro heart muscle model confirmed the antiapoptotic effects of miR-133a-CPCs, favoring the structuration and contractile functionality of the artificial tissue.