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Original Research

Open Access

COL3A1 induces ischemic heart failure by activating AGE/RAGE pathway

  • Xiao Chen1,2
  • Jiawei Zhang2
  • Tong Li2
  • Zhaosheng Ding2
  • Cao Zou1,*,

1Department of Cardiology, The First Affiliated Hospital of Soochow University, 215006 Suzhou, Jiangsu, China

2Department of Cardiopulmonary Rehabilitation, Jiangsu Rongjun Hospital, 214000 Wuxi, Jiangsu, China

DOI: 10.22514/sv.2022.072 Vol.18,Issue 6,November 2022 pp.45-52

Submitted: 06 June 2022 Accepted: 26 July 2022

Published: 08 November 2022

*Corresponding Author(s): Cao Zou E-mail: nkzc75@suda.edu.cn

Abstract

This study aimed to screening different expression genes (DEGs) related to ischemic heart failure (IHF). For screening DEGs in gene omnibus (GEO) dataset, limma methods were used to screen the significant DEGs between IHF and sham groups. Venn plot was used for the analysis of the intersection DEGs among three GEO datasets (GSE107568, GSE107569, and GSE116250). String and KEGG (kyoto encyclopedia of genes and genomes) pathway were used for the analysis of key DEGs and their associated signal pathway. IHF rats model were established by high ligation of the anterior descending branch of the coronary artery. Functional indices were analyzed using echocardiography. IHF rats were then administrated with AAV-shCOL3A1 to knockdown its expression. The expression of COL3A1 was measured by RNA-sequencing and western blotting. Transmission electron microscope (TEM) assay was used to measure the apoptosis of cardiomyocytes. Serum AGE (advanced glycation end-products), SOD (superoxide dismutase), MDA (malondialdehyde), and LDH (lactate dehydrogenase) levels were determined by enzyme-linked immunosorbent assay (ELISA) kit. Limma analysis discovered 14 upregulated DEGs were involved in three GEO datasets (GSE107568, GSE107569, and GSE116250), and COL3A1 was identified as one of the key genes, which was associated with AGE/RAGE (receptor for advanced glycation end-products) pathway by KEGG enrichment analysis. Western blotting and RNA-Seq indicated that COL3A1 protein and mRNA were highly expressed in IHF rats model as compared to that in sham rats. Pathology photograph analysis showed that COL3A1 deficiency inhibited infarct size in IHF rats. In addition, knockdown of COL3A1 decreased cell apoptosis in IHF rats by transmission electron microscope (TEM) assay. Mechanically, COL3A1 deficiency inhibited IHF development through activating AGE/RAGE signal pathway. The present study suggests that COL3A1 induces IHF progression and development through activating AGE/RAGE pathway.


Keywords

Heart failure; COL3A1; AGE/RAGE pathway; Cell damage and apoptosis


Cite and Share

Xiao Chen,Jiawei Zhang,Tong Li,Zhaosheng Ding,Cao Zou. COL3A1 induces ischemic heart failure by activating AGE/RAGE pathway. Signa Vitae. 2022. 18(6);45-52.

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