OSM mitigates post-infarction cardiac remodeling and dysfunction by up-regulating autophagy through Mst1 suppression

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Regenerative Medicine

Background:

• Heart failure (HF) incidence is rising, often exacerbated by myocardial infarction (MI).
• Understanding post-MI cardiac remodeling mechanisms is crucial for developing effective therapies.
• Oncostatin M (OSM) role in cardiac repair post-MI requires elucidation.

Purpose of the Study:

• To investigate the effects of Oncostatin M (OSM) on cardiac remodeling and function following myocardial infarction (MI).
• To explore the underlying mechanisms, including cardiomyocyte autophagy and the OSM receptor (OSMR) pathway.
• To assess OSM's therapeutic potential in mitigating post-MI heart failure.

Main Methods:

• Myocardial infarction (MI) model induced by left anterior descending coronary artery (LAD) ligation in mice.
• In vitro studies using cultured neonatal mouse cardiomyocytes subjected to simulated MI.
• Assessment of cardiac function, left ventricular remodeling, and mitochondrial structure.
• Analysis of autophagic flux using Ad-GFP-LC3 and investigation of OSM receptor beta (OSMR) knockout effects.
• Evaluation in Mst1 transgenic and knockout mouse models.

Main Results:

• OSM treatment significantly alleviated left ventricular remodeling and improved cardiac function post-MI.
• OSM restored mitochondrial cristae density and corrected architectural abnormalities.
• Enhanced autophagic flux was observed in OSM-treated cardiomyocytes.
• OSM's beneficial effects were abolished in OSMR knockout mice.
• OSM pretreatment improved outcomes in Mst1 transgenic mice but had limited effect in Mst1 knockout mice.

Conclusions:

• Oncostatin M (OSM) ameliorates post-infarction cardiac remodeling and dysfunction.
• OSM enhances cardiomyocyte autophagy, a key mechanism for its protective effects.
• The OSM receptor beta (OSMR) is essential for mediating OSM's cardioprotective actions.
• OSM shows potential as a therapeutic target for treating heart failure post-MI, possibly via Mst1 pathway modulation.