Sarcopenia-derived exosomal micro-RNA 16-5p disturbs cardio-repair via a pro-apoptotic mechanism in myocardial...

Area of Science:

• Cardiovascular Biology
• Muscle Physiology
• Molecular Medicine

Background:

• Sarcopenia, linked to poor heart disease prognosis, lacks mechanistic understanding due to limited animal models.
• Cardiac cachexia associated with sarcopenia complicates heart disease management.
• The interplay between skeletal muscle atrophy and cardiac repair remains unclear.

Purpose of the Study:

• To establish a novel mouse model for sarcopenia-induced cardiac repair disturbance.
• To identify molecular mechanisms linking sarcopenia and impaired cardiac healing.
• To investigate the role of exosomal microRNAs in sarcopenia-related cardiac dysfunction.

Main Methods:

• Developed a tail suspension (TS) mouse model post-ischemia/reperfusion (I/R) to induce sarcopenia.
• Identified and quantified circulating exosomal miR-16-5p in I/R-TS mice.
• Utilized in vitro studies with neonatal rat ventricular myocytes (NRVMs) under hypoxic conditions and miR-16-5p mimic.

Main Results:

• The I/R-TS model successfully replicated sarcopenia-induced cardiac repair disturbance.
• Circulating exosomal miR-16-5p levels were elevated in I/R-TS mice, originating from atrophic muscles and the heart.
• miR-16-5p directly impaired cardiac repair in I/R mice and induced apoptosis in NRVMs via p53 and Caspase3, while inhibiting autophagy through mTOR activation.

Conclusions:

• Sarcopenia-derived miR-16-5p exhibits a pro-apoptotic effect, potentially worsening myocardial infarction.
• miR-16-5p is identified as a key mediator of cardiac repair disturbances in sarcopenia-cachexia.
• miR-16-5p represents a novel therapeutic target for managing cardiac complications in sarcopenia.