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Chrysin attenuates interstitial fibrosis and improves cardiac function in a rat model of acute myocardial infarction

Journal of Molecular Histology volume 49, pages 555–565 (2018)Cite this article

Abstract

Interstitial fibrosis after acute myocardial infarction (MI) leads to cardiac structural remodeling and dysfunction. The peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist chrysin has been shown to protect injured myocardium through suppression of oxidative stress and inflammation. This study was designed to investigate the effect and mechanism of chrysin on myocardial fibrosis. A rat MI model was created by ligating the left coronary artery. The rats with MI were treated with chrysin (40 mg/kg/day) or 0.5% carboxymethylcellulose sodium by intragastric administration for 4 weeks after operation. The effect of chrysin on cardiac fibroblasts (CFs) were also assessed in vitro. Echocardiography showed that cardiac function was significantly improved after chrysin treatment. Chrysin reduced the levels of MDA and SOD and GSH-Px in myocardial tissue. Chrysin attenuated the interstitial and perivascular fibrosis and the expression of collagenlin the peri-infarcted zone and remarkably decreased the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9. Chrysin up-regulated PPAR-γ and inhibited the nuclear factor-kappa B (NF-κB) pathway by suppressing inhibitor kappa B kinase β phosphorylation. Immunohistochemistry analysis and PCR detected downregulated expression of AP-1 after chrysin treatment. Chrysin also markedly reduced the increased α-SMA, typeland type III collagen expression of CFs mediated by AngII in vitro. In conclusion, chrysin has an antifibrosis cardioprotective effect on the infarct peripheral zone after MI. The underlined mechanism may be the up-regulation of PPAR-γ and inhibition of the NF-κB and AP1 pathway.

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Acknowledgements

We express our grateful thanks to our colleague Tao Liu, Renmin Hospital of Wuhan University, for carrying out the data analysis. This research was financially supported by the Fundamental Research Funds for the Central Universities (No. 2018413000185).

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Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei, People’s Republic of China

    Mei Yang, Qiang Zou, Dan-Dan Wang & Cong-Xin Huang

  2. Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People’s Republic of China

    Mei Yang, Qiang Zou, Dan-Dan Wang & Cong-Xin Huang

  3. Hubei Key Laboratory of Cardiology, Wuhan, 430060, People’s Republic of China

    Mei Yang, Qiang Zou, Dan-Dan Wang & Cong-Xin Huang

  4. Department of Emergency, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China

    Jun Xiong

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  1. Mei Yang
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Correspondence to Cong-Xin Huang.

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Yang, M., Xiong, J., Zou, Q. et al. Chrysin attenuates interstitial fibrosis and improves cardiac function in a rat model of acute myocardial infarction. J Mol Hist 49, 555–565 (2018). https://doi.org/10.1007/s10735-018-9793-0

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  • DOI: https://doi.org/10.1007/s10735-018-9793-0

Keywords

  • Chrysin
  • PPAR-γ
  • Interstitial fibrosis
  • Myocardial infarction
  • NF-κB
  • AP1