Heart failure & cardiomyopathies
Inhibition of Annexin A2 Facilitates PHB2-Mediated Mitophagy in Cardiomyocytes to Alleviate Cardiac Injury and Remodeling After Infarction
Authors' conclusion
These findings highlight the significance of ANXA2 inhibition as a molecular brake on mitophagy inactivation in cardiomyocytes under MI and uncover an ANXA2-mediated posttranslational mechanism essential for maintaining mitochondrial homeostasis and alleviating heart failure after MI.
Study context
- Population
- Myocardial infarction (MI) mice and neonatal rat ventricular myocytes; human ischemic failing hearts and patients with acute MI
- Comparison
- Cardiomyocyte-specific Anxa2 knockdown or overexpression in MI
Main finding
As reported in the abstract
- ANXA2 highly expressed in murine and human ischemic failing hearts; circulating ANXA2 positively correlated with cardiac injury in acute MI
- Cardiomyocyte-specific Anxa2 depletion averted mitophagy inactivation, oxidative stress, cell death and inflammatory infiltration, improving infarct size, heart function and remodeling after MI
- Anxa2 overexpression suppressed mitophagy, exacerbating cardiac injury and HF after MI
- ANXA2 bound PHB2, blocked LC3B–PHB2 binding and promoted TRIM29-mediated K48-linked polyubiquitination and proteasomal degradation of PHB2
- Phb2 knockdown abrogated the protective effects of Anxa2 deficiency in vitro and in vivo
Original publication
Inhibition of Annexin A2 Facilitates PHB2-Mediated Mitophagy in Cardiomyocytes to Alleviate Cardiac Injury and Remodeling After Infarction. Circulation. Published 6 January 2026. doi:10.
Summarised from the published abstract; every number is checked against it