Ethyl ferulate suppresses post-myocardial infarction myocardial fibrosis by inhibiting transforming growth factor receptor 1
- Phytomedicine. 2023 Dec:121:155118. doi: 10.1016/j.phymed.2023.155118.
- 1. Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, 250 Changgangdong Road, Guangzhou 510260, China.
- 2. School of Traditional Chinese Medicine, Department of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), Southern Medical University, Guangzhou 510515, China.
- 3. The Second Clinical School of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510260, China.
- 4. School of Traditional Chinese Medicine, Department of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
- 5. Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, 250 Changgangdong Road, Guangzhou 510260, China. Electronic address: [email protected].
- 6. Department of Traditional Chinese Medicine, Guangzhou Institute of Cardiovascular Disease, State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou Medical University, 250 Changgangdong Road, Guangzhou 510260, China. Electronic address: [email protected].
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.
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