1. Academic Validation
  2. Silencing RGS7 attenuates atrial fibrillation progression by activating the cGMP-PKG signaling pathway

Silencing RGS7 attenuates atrial fibrillation progression by activating the cGMP-PKG signaling pathway

  • Biochim Biophys Acta Mol Basis Dis. 2025 Mar 13;1871(5):167786. doi: 10.1016/j.bbadis.2025.167786.
Hao Huang 1 Yan Xiong 2 Jie Zeng 3
Affiliations

Affiliations

  • 1 Department of Cardiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu City, PR China.
  • 2 Institute of Cardiovascular Diseases & Department of Cardiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of, PR China.
  • 3 Department of Cardiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu City, PR China. Electronic address: jiezeng002@sina.com.
Abstract

Background: Atrial fibrillation (AF) is a common diagnosed heart disease that needs novel managements. This study aimed to seek potential biomarkers and underlying regulatory pathways associated with AF.

Methods: Differential expressed genes (DEGs) were identified from the Gene Expression Omnibus database, followed by a protein-protein interaction (PPI) network to discover hub genes. Principal components analysis (PCA) and receiver operating characteristic (ROC) curves were performed to evaluate the ability of hub genes to discriminate between AF and control. RGS7 was selected as a key hub gene, and genes co-expressed with RGS7 were identified for functional enrichment analysis. Further in vivo and in vitro experiments were conducted to investigate the effects of silencing RGS7 on AF and the potential pathway.

Results: We identified top 5 hub genes (RGS7, EGFR, RGS4, GNA13 and RGS11) from the PPI network. PCA showed these genes could distinguish between AF and control samples, with 100 % of the area under curve (AUC) values. Silencing RGS7 inhibited cell Apoptosis, inflammation and oxidative stress, and increased mitochondrial membrane potential in angiotensin II (AngII)-treated HL-1 cells, while overexpression of RGS7 reversed the inhibitory effects of silencing RGS7 on AF. Additionally, silencing RGS7 improved cardiac function and decreased cardiac fibrosis in AF rats. The cGMP-PKG signaling pathway was screened as a potential signal transduction pathway, and silencing RGS7 increased the expression of PKG1, while KT5823 blocked the process.

Conclusion: Silencing RGS7 attenuates AF by activating the cGMP-PKG signaling pathway, which may offer directions for selecting biomarkers and regulatory pathways for AF.

Keywords

Atrial fibrillation; Protein-protein interaction network; RGS7; cGMP-PKG.

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