2. Academic Validation
  3. CD44 alleviates myocardial ischemia reperfusion injury through repressing ferroptosis

CD44 alleviates myocardial ischemia reperfusion injury through repressing ferroptosis

  • Int Immunopharmacol. 2026 Mar 1:172:116230. doi: 10.1016/j.intimp.2026.116230.
Xia Huang 1,  Shu Wang 1,  Tingting Xue 1,  Yanni Wang 1,  Qin Yan 2,  Xinyu Zhu 1,  Huihui Li 2,  Fuheng Chen 3,  Yifei Zhang 3,  Xiangrong Cui 4,  Xuan Jing 5
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory of Shanxi Provincial People's Hospital, Shanxi Medical University, Taiyuan 030012,China.
  • 2 Reproductive Medicine Center, The affiliated Children's Hospital of Shanxi Medical University, Children's Hospital of Shanxi, Women Health Center of Shanxi, Taiyuan 030001, China.
  • 3 The Cardiology Department of Shanxi Provincial People's Hospital, Shanxi Medical University, Taiyuan 030012, China.
  • 4 Reproductive Medicine Center, The affiliated Children's Hospital of Shanxi Medical University, Children's Hospital of Shanxi, Women Health Center of Shanxi, Taiyuan 030001, China. Electronic address: [email protected].
  • 5 Department of Clinical Laboratory of Shanxi Provincial People's Hospital, Shanxi Medical University, Taiyuan 030012,China. Electronic address: [email protected].
PMID: 41564476 DOI: 10.1016/j.intimp.2026.116230
Abstract

Background: Myocardial ischemia-reperfusion injury(MIRI) is a significant contributor to poor prognosis after myocardial infarction. Ferroptosis, a novel form of regulated cell death, is involved in MIRI. However, the role of Ferroptosis in the ischemia phase and reperfusion phase remains unclear, and key regulatory mechanisms still need further exploration.

Methods and results: AC16 cardiomyocyte oxygen-glucose deprivation/reoxygenation (OGD/R) model and mice MIRI model were established to investigate the role of Ferroptosis in ischemia phase and reperfusion phase, our study found that Ferroptosis occurred more prominently during the reperfusion phase than the ischemia phase. Therefore, in subsequent studies, we primarily focused on the role of Ferroptosis in myocardial reperfusion injury phase rather than the ischemia phase alone. Through integrated bioinformatics analysis, we identified CD44 as the hub gene of Ferroptosis. Venous blood samples and clinical information were collected from patients with acute myocardial infarction (AMI). Moreover, a loss-of-function approach was conducted to understand the role of CD44 in MIRI. CD44 expression was upregulated during the reperfusion phase, but not the ischemia phase. AMI patients who underwent Percutaneous Coronary Intervention (PCI) had higher plasma CD44 levels compared to those who did not undergo PCI and healthy individuals. Plasma CD44 levels of post-PCI was closely correlated with adverse prognostic indicators of MI. Knockdown of CD44 markedly aggravated cardiomyocyte injury and Ferroptosis by regulating the stability of SLC7A11, at least to some extent.

Conclusion: Our results uncover the cardioprotective role of CD44 by attenuating Ferroptosis during MIRI. Targeting CD44- initiated signaling may serve as a promising therapeutic target for MIRI.

Keywords

Bioinformatics; CD44; Ferroptosis; Myocardial ischemia reperfusion.

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