Cardiomyocyte IL-1R2 protects heart from ischemia/reperfusion injury by attenuating IL-17RA-mediated cardiomyocyte apoptosis

  • Cell Death Dis. 2022 Jan 27;13(1):90. doi: 10.1038/s41419-022-04533-1.
Jun Lin   #  1  2 ,  Qinfeng Li   #  1  2 ,  Tingting Jin   #  1  2 ,  Jiacheng Wang  1  2 ,  Yingchao Gong  1  2 ,  Qingbo Lv  1  2 ,  Meihui Wang  1  2 ,  Jiawen Chen  1  2 ,  Min Shang  3  4 ,  Yanbo Zhao  5  6 ,  Guosheng Fu  7  8
Affiliations
  • 1. Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
  • 2. Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Hangzhou, China.
  • 3. Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. [email protected].
  • 4. Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Hangzhou, China. [email protected].
  • 5. Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. [email protected].
  • 6. Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Hangzhou, China. [email protected].
  • 7. Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. [email protected].
  • 8. Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Hangzhou, China. [email protected].
  • # Contributed equally.
PMID: 35087030 DOI: 10.1038/s41419-022-04533-1
Abstract

Myocardial ischemia reperfusion (I/R) injury is a complex process with intense inflammatory response and cardiomyocyte Apoptosis. As a decoy receptor of IL-1β, Interleukin-1 receptor type 2 (IL-1R2) inhibits IL-1β signaling. However, its role in I/R injury remains unknown. Here we found that the serum levels of IL-1R2 were significantly increased in patients with acute myocardial infarction (AMI) following interventional therapy. Similarly, after myocardial I/R surgery, IL-1R2 expression was significantly increased in heart of wild-type mice. In addition, IL-1R2-deficient mice heart showed enlarged infarct size, increased cardiomyocyte Apoptosis together with reduced cardiac systolic function. Following exposure to hypoxia and reoxygenation (H/R), neonatal rat ventricular myocytes (NRVM) significantly increased IL-1R2 expression relying on NF-κB activation. Consistently, IL-1R2-deficient mice increased immune cells infiltrating into heart after surgery, which was relevant with cardiac damage. Additionally, IL-1R2 overexpression in cardiomyocyte protected cardiomyocyte against Apoptosis through reducing the IL-17RA expression both in vivo and in vitro. Our results indicate that IL-1R2 protects cardiomyocytes from Apoptosis, which provides a therapeutic approach to turn down myocardial I/R injury.

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