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Pirfenidone improves early cardiac function following myocardial infarction by enhancing the elastin/collagen ratio

Yu Y 1 , Xu Y 2 , Chen J 3 , Yao Y 4 , Liu Y 5 , Chen Y 6 Show all authors , Yang B 7 , Guo Z 8

Affiliations 

  • 1 Henan Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou Seventh People's Hospital, Zhengzhou, Henan 450016, China; Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan 453003, China. Electronic address: 544892985@qq.com
  • 2 Henan Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou Seventh People's Hospital, Zhengzhou, Henan 450016, China; USM-ALPS Cardiac Research Laboratory, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang 13200, Malaysia. Electronic address: xuyaping@student.usm.my
  • 3 Henan Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou Seventh People's Hospital, Zhengzhou, Henan 450016, China. Electronic address: 402875646@qq.com
  • 4 Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan 453003, China. Electronic address: 64996253@qq.com
  • 5 Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan 453003, China. Electronic address: 1123368560@qq.com
  • 6 Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan 453003, China. Electronic address: 448202359@qq.com
  • 7 Henan Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou Seventh People's Hospital, Zhengzhou, Henan 450016, China. Electronic address: yangbin166@163.com
  • 8 Henan Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou Seventh People's Hospital, Zhengzhou, Henan 450016, China; Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan 453003, China. Electronic address: gzk@xxmu.edu.cn
Biomed Pharmacother, 2024 Sep;178:117254.
PMID: 39142250 DOI: 10.1016/j.biopha.2024.117254

Abstract

BACKGROUND: Acute myocardial infarction (AMI) is a leading cause of mortality worldwide, with reduced elastin/collagen ratios exacerbating cardiac dysfunction due to collagen-rich scar tissue replacing necrotic myocardial cells. This study aims to evaluate pirfenidone's therapeutic effect on early cardiac function post-AMI and elucidate its impact on the elastin/collagen ratio.

METHODS: Sprague-Dawley rats were divided into four groups: Sham, AMI, AMI treated with PBS (AMI-PBS), and AMI treated with pirfenidone (AMI-PFD) (n=12 each). AMI was induced via coronary artery ligation. The AMI-PFD and AMI-PBS groups received pirfenidone and PBS for 14 days, respectively. Cardiac function, fibrosis, serum cytokines, collagen and elastin content, and their ratios were assessed. Cardiac fibroblasts (CFs) from neonatal rats were categorized into control, hypoxia-induced (LO), LO+PBS, and LO+PFD groups. ELISA measured inflammatory factors, and RT-PCR analyzed collagen and elastin gene expression.

RESULTS: The AMI-PFD group showed improved cardiac function and reduced serum interleukin-1β (IL-1β), IL-6, and transforming growth factor-β (TGF-β). Type I and III collagen decreased by 22.6 % (P=0.0441) and 34.4 % (P=0.0427), respectively, while elastin content increased by 79.4 % (P=0.0126). E/COLI and E/COLIII ratios rose by 81.1 % (P=0.0026) and 88.1 % (P=0.0006). CFs in the LO+PFD group exhibited decreased IL-1β, IL-6, TGF-β, type I and III collagen, with increased elastin mRNA, enhancing the elastin/collagen ratio.

CONCLUSION: Pirfenidone enhances cardiac function by augmenting the early elastin/collagen ratio post-AMI.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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