Cardiosomal microRNAs are essential in post-infarction myofibroblast phenoconversion

Marco B. Morelli, Jun Shu, Celestino Sardu, Alessandro Matarese, Gaetano Santulli

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The inclusion of microRNAs (miRNAs) in extracellular microvesicles/exosomes (named cardiosomes when deriving from cardiomyocytes) allows their active transportation and ensures cell-cell communication. We hypothesize that cardiosomal miRNAs play a pivotal role in the activation of myofibroblasts following ischemic injury. Using a murine model of myocardial infarction (MI), we tested our hypothesis by measuring in isolated fibroblasts and cardiosomes the expression levels of a set of miRNAs, which are upregulated in cardiomyocytes post-MI and involved in myofibroblast phenoconversion. We found that miR-195 was significantly upregulated in cardiosomes and in fibroblasts isolated after MI compared with SHAM conditions. Moreover, primary isolated cardiac fibroblasts were activated both when incubated with cardiosomes isolated from ischemic cardiomyocytes and when cultured in conditioned medium of post-MI cardiomyocytes, whereas no significant effect was observed following incubation with cardiosomes or medium from sham cardiomyocytes. Taken together, our findings indicate for the first time that a cardiomyocyte-specific miRNA, transferred to fibroblasts in form of exosomal cargo, is crucial in the activation of myofibroblasts.

Original languageEnglish (US)
Article number201
JournalInternational Journal of Molecular Sciences
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • Cardiac ischemia
  • Epigenetics
  • Exosomes
  • Extracellular vesicles
  • Fibroblasts
  • Inflammation
  • MicroRNA
  • Myocardial infarction
  • Myofibroblast activation

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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