Downregulation of SIRT1 and GADD45G genes and left atrial fibrosis induced by right ventricular dependent pacing in a complete atrioventricular block pig model

Authors

  • Wei-Chieh Lee Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Cardiology, Chi Mei Medical Center, Tainan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan; Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
  • Yu-Sheng Lin Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
  • Man-Jing Chen Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
  • Wan-Chun Ho Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
  • Huang-Chung Chen Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
  • Tzu-Hao Chang Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei, Taiwan
  • Ping-Yen Liu Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  • Mien-Cheng Chen Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan

DOI:

https://doi.org/10.17305/bb.2023.9636

Keywords:

Atrial fibrosis, atrioventricular block, sirtuin signaling pathway, SIRT1, right ventricular pacing

Abstract

The molecular and genetic mechanisms underlying left atrial (LA) enlargement and atrial fibrosis following right ventricular (RV) dependent pacing remain unclear. Our objective was to investigate genetic expressions in the LA of pigs subjected to RV pacing for atrioventricular block (AVB), as well as to identify the differential gene expressions affected by biventricular (BiV) pacing. We established an AVB pig model and divided the subjects into three groups: a sham control group, an RV pacing group, and a BiV pacing group. Differential expression genes (DEGs) analyses conducted through next-generation sequencing (NGS) and enrichment analyses were employed to identify genes with altered expression in the LA myocardium. The RV pacing group showed a significant increase in extracellular fibrosis in the LA myocardium compared to the control group. NGS analysis revealed suppressed expression of the sirtuin signaling pathway in the RV pacing group. Among the DEGs within this pathway, GADD45G was found to be downregulated in the RV pacing group and upregulated in the BiV pacing group. Remarkably, the BiV pacing group exhibited elevated levels of GADD45G protein. In our study, we observed significant downregulation of SIRT1 and GADD45G genes, which are associated with the sirtuin signaling pathway, in the LA myocardium of the RV pacing group when compared to the control group. Moreover, these genes, which were downregulated in the RV pacing group, displayed a noteworthy upregulation in the BiV pacing group when compared to the RV pacing group.

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Downregulation of SIRT1 and GADD45G genes and left atrial fibrosis induced by right ventricular dependent pacing in a complete  atrioventricular block pig model

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Published

11-03-2024

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Section

Translational and Clinical Research

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How to Cite

1.
Downregulation of SIRT1 and GADD45G genes and left atrial fibrosis induced by right ventricular dependent pacing in a complete atrioventricular block pig model. Biomol Biomed [Internet]. 2024 Mar. 11 [cited 2024 Apr. 18];24(2):360–373. Available from: https://bjbms.org/ojs/index.php/bjbms/article/view/9636