CircCOL3A1 ameliorates myocardial ischemia-reperfusion injury by regulating miR-29b-3p/MDM2-mediated apoptosis.

Background: Cardiovascular diseases (CVDs) are leading causes of mortality globally, with myocardial ischemia-reperfusion (I/R) injury being a critical challenge in clinical settings. Circular RNAs (circRNAs) have emerged as significant molecular players in various pathophysiological conditions, including myocardial I/R injury.

Objective: This study aimed to investigate the role of circCOL3A1 in myocardial I/R injury and its potential regulatory mechanisms involving miR-29b-3p and MDM2.

Methods: Using a mouse model and H9c2 cardiomyocyte cells, we examined the expression levels of circCOL3A1 under I/R and hypoxia/reoxygenation (H/R) conditions. We utilized RT-qPCR, Western blotting, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and dual-luciferase reporter assays to explore the interaction between circCOL3A1, miR-29b-3p, and MDM2.

Results: CircCOL3A1 was significantly downregulated in both I/R-treated mice and H/R-treated H9c2 cells. Overexpression of circCOL3A1 reduced apoptosis and improved cell viability by modulating the miR-29b-3p/MDM2 axis. These effects were reversed by overexpressing miR-29b-3p or silencing MDM2.

Conclusion: CircCOL3A1 plays a protective role in myocardial I/R injury by acting as a miR-29b-3p sponge, thereby regulating the MDM2-mediated apoptosis pathway. This identifies circCOL3A1 as a potential therapeutic target for treating myocardial I/R injury.