2. Academic Validation
  3. Upregulation of CIRP by its agonist prevents the development of heart failure in myocardial infarction rats

Upregulation of CIRP by its agonist prevents the development of heart failure in myocardial infarction rats

  • BMC Cardiovasc Disord. 2024 Mar 27;24(1):185. doi: 10.1186/s12872-024-03852-9.
Jingjing Zhang # 1 2 3,  Tao Liu # 1 2 3,  Yanzhao Wei 1 2 3,  Jianye Peng 4 5 6,  Gaofeng Zeng 7 8 9,  Peng Zhong 10 11 12
Affiliations

Affiliations

  • 1 Department of Cardiology Research Institute, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei, 430060, China.
  • 2 Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China.
  • 3 Hubei Key Laboratory of Cardiology, Wuhan, 430060, China.
  • 4 The Second Affiliated Hospital, Department of Cardiovascular Medicine, Hengyang Medical School, University of South China, Hengyang, China.
  • 5 The Second Affiliated Hospital, Key laboratory of Heart Failure Prevention & Treatment of Hengyang, Hengyang Medical School, University of South China, Hengyang, 421001, China.
  • 6 Clinical Medicine Research Center of Arteriosclerotic Disease of Hunan Province, University of South China, Hengyang, 421001, China.
  • 7 The Second Affiliated Hospital, Department of Cardiovascular Medicine, Hengyang Medical School, University of South China, Hengyang, China. [email protected].
  • 8 The Second Affiliated Hospital, Key laboratory of Heart Failure Prevention & Treatment of Hengyang, Hengyang Medical School, University of South China, Hengyang, 421001, China. [email protected].
  • 9 Clinical Medicine Research Center of Arteriosclerotic Disease of Hunan Province, University of South China, Hengyang, 421001, China. [email protected].
  • 10 Department of Cardiology Research Institute, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei, 430060, China. [email protected].
  • 11 Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China. [email protected].
  • 12 Hubei Key Laboratory of Cardiology, Wuhan, 430060, China. [email protected].
  • # Contributed equally.
PMID: 38539067 DOI: 10.1186/s12872-024-03852-9
Abstract

Background: Downregulated expression of cold-inducible RNA binding protein (CIRP), a stress-response protein, has been demonstrated in the hearts of patients with heart failure (HF). However, whether CIRP plays a critical role in the pathogenesis of HF remains unknown. Zr17-2 is a recently identified CIRP agonist, which can enhance the expression of CIRP in hearts. Herein, we evaluated the effects of zr17-2 on the development of HF in a rat model of myocardial infarction (MI).

Methods: Male SD rats were pretreated with CIRP agonist zr17-2 or vehicle saline for 6 consecutive days, followed by MI induction. 1-week post-MI, cardiac function, and structural and molecular changes were determined by echocardiography and Molecular Biology methods.

Results: Excitingly, we found that pretreatment with zr17-2 significantly attenuated MI-induced cardiac dysfunction and dilation, coupled with reduced infarction size and cardiac remodeling. In addition, increased inflammatory response in the peri-infarcted heart including macrophage infiltration and the expression of inflammatory genes were all significantly decreased by zr17-2 pretreatment, suggesting an anti-inflammatory effect of zr17-2. Moreover, zr17-2 pretreatment also upregulated the antioxidant genes (e.g. NQO-1, Nrf2, and HO-1) level in the hearts. In isolated cultured cardiomyocytes, pretreatment with zr17-2 markedly attenuated cell injury and Apoptosis induced by oxidative injury, along with elevation of Nrf2-related antioxidant genes and CIRP. However, silencing CIRP abolished zr17-2's antioxidant effects against oxidative injury, confirming that zr17-2's role is dependent on CIRP.

Conclusion: Collectively, our study suggests CIRP plays a crucial role in the development of HF and a beneficial effect of CIRP agonist in preventing MI-induced HF, possibly via anti-inflammatory and anti-oxidant pathways.

Keywords

CIRP; Inflammation; Myocardial infarction; Nrf2; zr17-2.

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