Ethyl ferulate suppresses post-myocardial infarction myocardial fibrosis by inhibiting transforming growth factor receptor 1.

Abstract

BACKGROUND:

With an increasing number of myocardial infarction (MI) patients, myocardial fibrosis is becoming a widespread health concern. It's becoming more and more urgent to conduct additional research and investigations into efficient treatments. Ethyl ferulate (EF) is a naturally occurring substance with cardioprotective properties. However, the extent of its impact and the underlying mechanism of its treatment for myocardial fibrosis after MI remain unknown.

PURPOSE:

The goal of this study was to look into how EF affected the signaling of the TGF-receptor 1 (TGFBR1) in myocardial fibrosis after MI.

METHODS:

Echocardiography, hematoxylin-eosin (HE) and Masson trichrome staining were employed to assess the impact of EF on heart structure and function in MI-affected mice in vivo. Cell proliferation assay (MTS), 5-Ethynyl-2'-deoxyuridine (EdU), and western blot techniques were employed to examine the influence of EF on native cardiac fibroblast (CFs) proliferation and collagen deposition. Molecular simulation and surface plasmon resonance imaging (SPRi) were utilized to explore TGFBR1 and EF interaction. Cardiac-specific Tgfbr1 knockout mice (Tgfbr1ΔMCK) were utilized to testify to the impact of EF.

RESULTS:

In vivo experiments revealed that EF alleviated myocardial fibrosis, improved cardiac dysfunction after MI and downregulated the TGFBR1 signaling in a dose-dependent manner. Moreover, in vitro experiments revealed that EF significantly inhibited CFs proliferation, collagen deposition and TGFBR1 signaling followed by TGF-β1 stimulation. More specifically, molecular simulation, molecular dynamics, and SPRi collectively showed that EF directly targeted TGFBR1. Lastly, knocking down of Tgfbr1 partially reversed the inhibitory activity of EF on myocardial fibrosis in MI mice.

CONCLUSION:

EF attenuated myocardial fibrosis post-MI by directly suppressing TGFBR1 and its downstream signaling pathway.

• Authors: Ke-Feng Zeng, Hui-Juan Wang, Bo Deng, Ting-Fang Chen, Jun-Bang Chen, Wen-Jun Ding, Si Chen, Jun-di Xie, Si-Min Lu, Guang-Hong Chen, Ying Zhang, Zhang-Bin Tan, Hong-Bin Ou, Yong-Zhen Tan, Shuang-Wei Zhang, Ying-Chun Zhou, Jing-Zhi Zhang, Bin Liu
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 121 Pg. 155118 (Dec 2023) ISSN: 1618-095X [Electronic] Germany
• PMID: 37801895 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier GmbH. All rights reserved.

Chemical References

• Receptor, Transforming Growth Factor-beta Type I
• ethyl ferulate
• Collagen
• Transforming Growth Factor beta1

Topics

• Humans
• Mice
• Animals
• Myocardium (metabolism)
• Receptor, Transforming Growth Factor-beta Type I (metabolism, therapeutic use)
• Fibroblasts (metabolism)
• Myocardial Infarction (drug therapy, metabolism)
• Collagen (metabolism)
• Fibrosis
• Transforming Growth Factor beta1 (metabolism)