STEMIN- and YAP5SA-induced exosomes prevent cardiomyocyte apoptosis.

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Regenerative Medicine

Background:

• Cardiac regeneration research focuses on transient reprogramming to repair heart damage.
• Cardiomyocyte function decline is often linked to apoptosis.

Purpose of the Study:

• To investigate the effects of STEMIN and YAP5SA modRNA delivery on cardiomyocyte reprogramming and survival.
• To elucidate the mechanisms underlying apoptosis resistance induced by this reprogramming strategy.

Main Methods:

• Delivery of modRNA encoding STEMIN and YAP5SA to rat and human cardiomyocytes.
• Chromatin remodeling and transcriptional profiling using ATAC-seq and RNA-seq.
• Exosome profiling and functional assays for apoptosis assessment in vitro and in vivo.

Main Results:

• STEMIN and YAP5SA induced coordinated chromatin remodeling and transcriptional reprogramming.
• Activation of cell cycle, DNA replication, and survival pathways observed.
• Upregulation of microRNAs conferring apoptosis resistance, packaged in exosomes.
• Demonstrated reduction in cardiomyocyte apoptosis both in vitro and in vivo.

Conclusions:

• modRNA-mediated delivery of STEMIN and YAP5SA promotes cardiomyocyte survival by inhibiting apoptosis.
• Exosomal microRNAs play a key role in mediating the anti-apoptotic effects.
• This strategy presents a potential therapeutic framework for cardiac repair integrating modRNA and paracrine signaling.