| Summary: | Background: Acute myocardial infarction (AMI) continues to be a leading cause of morbidity and death. Objective: This study investigates miR-130's regulatory mechanisms in AMI progression. Methods: Bioinformatics analysis of miR-130 conservation and differential expression was performed using miRbase and Gene Expression Omnibus datasets. Angiotensin II (Ang II)-treated H9C2 cardiomyocytes modeled AMI in vitro. miR-130 inhibitor/mimic transfection, combined with autophagy inhibitor Spautin-1 or ferroptosis inhibitor Ferrostatin-1, were assessed via qPCR, ELISA (PC III, HA, CTnT, CK-MB), Western blot (LC3-II/LC3-I, p62, SLC7A11, GPX4), and flow cytometry. Results: Our results demonstrate that Ang II stimulation significantly elevates miR-130 expression in H9C2 cells, concomitant with increased secretion of myocardial injury and fibrosis markers. Inhibition of miR-130 markedly improved cell viability and reduced apoptosis, accompanied by decreased expression of fibrosis markers such as α-SMA and Collagen I, and a rebalancing of autophagy dynamics, as indicated by an increased LC3-II/LC3-I ratio and elevated p62 levels. Conversely, miR-130 overexpression via a synthetic mimic reduced cell viability and enhanced apoptosis, with a corresponding rise in fibrosis markers (PC III, HA, CTnT, CK-MB) and disruption of both autophagy and ferroptosis pathways, evidenced by decreased levels of SLC7A11 and GPX4. Notably, the adverse effects induced by miR-130 mimic were effectively reversed by Spautin-1 and Ferrostatin-1 co-treatment, suggesting that miR-130 modulates AMI-related cellular responses through intertwined autophagy and ferroptosis mechanisms. Conclusion: These findings reveal that miR-130 is a pivotal regulator of myocardial injury in AMI, mediating its effects via the modulation of autophagy and ferroptosis pathways. Targeting miR-130 may therefore represent a promising therapeutic strategy for mitigating myocardial damage and improving cardiac function following AMI.
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