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Shexiang Tongxin Dropping Pill Allieviates Heart Failure via Extracellula Matrix-Receptor Interaction Pathways Based on RNA-Seq Transcriptomics and Experimental Studies

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Abstract

Objective

To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills (STDP) on heart failure (HF).

Methods

Isoproterenol (ISO)-induced HF rat model and angiotensin II (Ang II)-induced neonatal rat cardiac fibroblast (CFs) model were used in the present study. HF rats were treated with and without STDP (3 g/kg). RNA-seq was performed to identify differentially expressed genes (DEGs). Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson’s stainings were taken to assess cardiac fibrosis. The levels of collagen I (Col I) and collagen III (Col III) were detected by immunohistochemical staining. CCK8 kit and transwell assay were implemented to test the CFs’ proliferative and migratory activity, respectively. The protein expressions of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9, Col I, and Col III were detected by Western blotting.

Results

The results of RNA-seq analysis showed that STDP exerted its pharmacological effects on HF via multiple signaling pathways, such as the extracellular matrix (ECM)-receptor interaction, cell cycle, and B cell receptor interaction. Results from in vivo experiments demonstrated that STDP treatment reversed declines in cardiac function, inhibiting myocardial fibrosis, and reversing increases in Col I and Col III expression levels in the hearts of HF rats. Moreover, STDP (6, 9 mg/mL) inhibited the proliferation and migration of CFs exposed to Ang II in vitro (P<0.05). The activation of collagen synthesis and myofibroblast generation were markedly suppressed by STDP, also the synthesis of MMP-2 and MMP-9, as well as ECM components Col I, Col III, and α-SMA were decreased in Ang II-induced neonatal rats’ CFs.

Conclusions

STDP had anti-fibrotic effects in HF, which might be caused by the modulation of ECM-receptor interaction pathways. Through the management of cardiac fibrosis, STDP may be a compelling candidate for improving prognosis of HF.

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Authors and Affiliations

  1. Intensive Care Research Team of Traditional Chinese Medicine, Guangdong Province Hospital of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China

    Ya-fang Tan & Min-zhou Zhang

  2. School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, 510006, China

    Yu-han Fu

Authors
  1. Ya-fang Tan
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Corresponding author

Correspondence to Min-zhou Zhang.

Additional information

Supported by Foundation of Guangdong Province of Traditional Chinese Medicine (No. 20201142) and Medical Scientific Research Foundation of Guangdong Province (No. A2020323)

Conflict of Interest

The authors declare that they have no conflicts of interest.

Author Contributions

Zhang MZ conceived and designed the experiments, Tan YF and Fu YH performed the experiments, Tan YF analyzed the data, Fu YH contributed reagents/materials/analysis tools. Zhang MZ and Tan YF wrote the manuscript. All authors read and approved the final version of the manuscript.

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Tan, Yf., Fu, Yh. & Zhang, Mz. Shexiang Tongxin Dropping Pill Allieviates Heart Failure via Extracellula Matrix-Receptor Interaction Pathways Based on RNA-Seq Transcriptomics and Experimental Studies. Chin. J. Integr. Med. 29, 600–607 (2023). https://doi.org/10.1007/s11655-023-3633-0

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