PDCD4 exacerbates myocardial ischemia-reperfusion injury via AKT-mediated apoptosis

  • Cell Signal. 2025 Nov:135:111999. doi: 10.1016/j.cellsig.2025.111999.
Zhiming Zhang  1 ,  Zhihui Yang  1 ,  Hangbin Ge  1 ,  Chenyang Liu  1 ,  Renchenghan Fan  1 ,  Chenying Yuan  2 ,  Shengban You  3 ,  Chenglv Hong  4
Affiliations
  • 1. Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 2. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 3. Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: [email protected].
  • 4. Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: [email protected].
PMID: 40712690 DOI: 10.1016/j.cellsig.2025.111999
Abstract

Myocardial ischemia-reperfusion (I/R) injury is a critical complication following reperfusion therapy for myocardial infarction. As a marker of I/R injury, Apoptosis plays an important role in myocardial ischemia-reperfusion injury. Programmed Cell Death 4 (PDCD4) regulates Apoptosis in MI/RI, but the mechanism is not yet fully elucidated. In this study, we demonstrate that PDCD4 expression was significantly upregulated in a myocardial I/R injury model. Genetic deletion of PDCD4 markedly reduced infarct size, serum biomarkers of injury (CK-MB, cTnT, LDH), and Apoptosis in vivo. Mechanistically, PDCD4 directly interacts with Akt, inhibiting its phosphorylation by reducing ubiquitination. This suppression of Akt activity decreased Bcl-2 levels, promoting mitochondrial Apoptosis. Silencing PDCD4 restored Akt phosphorylation, attenuated Apoptosis, and alleviated myocardial damage. Our findings establish PDCD4 as a key driver of myocardial I/R injury via AKT-mediated Apoptosis and highlight its therapeutic potential.

Keywords
AKT signaling; Apoptosis; Myocardial ischemia-reperfusion injury; PDCD4; Ubiquitination.
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