Cardiosomal microRNAs Are Essential in Post-Infarction Myofibroblast Phenoconversion

Area of Science:

• Cardiovascular Biology
• Cellular Communication
• Molecular Medicine

Background:

• MicroRNAs (miRNAs) within extracellular microvesicles, termed cardiosomes from cardiomyocytes, facilitate intercellular communication.
• Cardiomyocyte-specific miRNAs are implicated in post-myocardial infarction (MI) cardiac remodeling.
• The role of cardiosomal miRNAs in activating cardiac myofibroblasts following ischemic injury remains largely unexplored.

Purpose of the Study:

• To investigate the hypothesis that cardiosomal miRNAs are pivotal in activating cardiac myofibroblasts after ischemic injury.
• To determine if specific miRNAs upregulated in cardiomyocytes post-MI are transferred via cardiosomes to fibroblasts.
• To elucidate the functional impact of these transferred miRNAs on fibroblast activation.

Main Methods:

• Utilized a murine model of myocardial infarction (MI).
• Isolated cardiac fibroblasts and cardiosomes from both MI and SHAM groups.
• Quantified miRNA expression levels in cardiosomes and fibroblasts using quantitative PCR.
• Assessed cardiac fibroblast activation upon incubation with cardiosomes or conditioned medium from post-MI cardiomyocytes.

Main Results:

• miR-195 was significantly upregulated in cardiosomes and cardiac fibroblasts isolated from MI mice compared to SHAM controls.
• Incubation with cardiosomes from ischemic cardiomyocytes or conditioned medium from post-MI cardiomyocytes activated primary cardiac fibroblasts.
• No significant fibroblast activation was observed with cardiosomes or medium from sham (control) conditions.

Conclusions:

• Cardiomyocyte-derived exosomes (cardiosomes) actively transport specific miRNAs.
• A cardiomyocyte-specific miRNA, miR-195, transferred via exosomal cargo, is crucial for activating cardiac myofibroblasts post-MI.
• This study reveals a novel mechanism of cell-cell communication in cardiac injury response mediated by exosomal miRNAs.