Autophagy-Related Genes in Atherosclerosis.

Yuankun Chen,Wenjie Mei,Shumiao He,Qun Lu,Ao Zeng,Siqing He,Chunmei Li,Hassène Gritli

doi:10.1155/2021/6402206

Abstract

Background Atherosclerosis (AS) is a common chronic vascular inflammatory disease and one of the main causes of cardiovascular/cerebrovascular diseases (CVDs). Autophagy-related genes (ARGs) play a crucial part in pathophysiological processes of AS. However, the expression profile of ARGs has rarely been adopted to explore the relationship between autophagy and AS. Therefore, using the expression profile of ARGs to explore the relationship between autophagy and AS may provide new insights for the treatment of CVDs. Methods The differentially expressed ARGs of the GSE57691 dataset were obtained from the Human Autophagy Database (HADb) and the Gene Expression Omnibus (GEO) database, and the GSE57691 dataset contains 9 aortic atheroma tissues and 10 normal aortic tissues. The differentially expressed ARGs of the GSE57691 dataset were analyzed by protein-protein interaction (PPI), gene ontology analysis (GO), and Kyoto Encyclopedia of Genes and Genomes analysis (KEGG) and were chosen to explore related miRNAs/transcriptional factors. Results The GSE57691 dataset had a total of 41 differentially expressed ARGs. The GO analysis results revealed that ARGs were mainly enriched in autophagy, autophagosome, and protein serine/threonine kinase activity. KEGG analysis results showed that ARGs were mainly enriched in autophagy-animal and longevity regulating signaling pathways. Expressions of ATG5, MAP1LC3B, MAPK3, MAPK8, and RB1CC1 were regarded as focus in the PPI regulatory networks. Furthermore, 11 related miRNAs and 6 related transcription factors were obtained by miRNAs/transcription factor target network analysis. Conclusions Autophagy and ARGs may play a vital role in regulating the pathophysiology of AS.

Highlights

Autophagy, a capacity of maintaining cellular homeostasis, is a process of damaging cytosolic material and delivering to lysosomes for degradation, leading to the turnover of cell material and providing macromolecular precursors [1, 2]
Based on the gene ontology analysis (GO) analysis, we found that the biological processes of differentially expressed Autophagy-related genes (ARGs) were markedly enriched in autophagy, process utilizing autophagic mechanism, and macroautophagy. e cell components of differentially expressed ARGs were markedly enriched in autophagosome, vacuolar membrane, and phagophore assembly site membrane. e molecular function of differentially expressed ARGs was markedly enriched in protein serine/ threonine kinase activity, MAP kinase activity, and ubiquitin protein ligase binding (Figure 3(a)). e results of the Kyoto Encyclopedia of Genes and Genomes analysis (KEGG) analysis showed that differentially expressed ARGs were primarily enriched in the autophagy-animal signaling pathway and longevity regulating signaling pathway (Figure 3(b))
Based on GO and KEGG analysis, we found that differentially expressed ARGs involve multiple biological processes and signaling pathways, including autophagy, autophagosome, and autophagy-animal signaling pathway

Summary

Introduction

A capacity of maintaining cellular homeostasis, is a process of damaging cytosolic material and delivering to lysosomes for degradation, leading to the turnover of cell material and providing macromolecular precursors [1, 2]. In the early stage of atherosclerotic lesions, autophagy can inhibit the apoptosis of vascular endothelial cells and delay the development of atherosclerotic plaques. In the late stage of atherosclerotic lesions, excessive activation of autophagy leads to autophagic death of vascular cells, decreased collagen synthesis, and weak fibrous caps that cause plaque rupture. The expression profile of ARGs has rarely been adopted to explore the relationship between autophagy and AS. Erefore, using the expression profile of ARGs to explore the relationship between autophagy and AS may provide new insights for the treatment of CVDs. Methods. E GSE57691 dataset had a total of 41 differentially expressed ARGs. e GO analysis results revealed that ARGs were mainly enriched in autophagy, autophagosome, and protein serine/threonine kinase activity. KEGG analysis results showed that ARGs were mainly enriched in autophagy-animal and longevity regulating signaling pathways. Autophagy and ARGs may play a vital role in regulating the pathophysiology of AS

Methods

Results

Discussion

Conclusion