Bioinformatics-based Identification and Validation of Hub Genes Associated with Aging in Patients with Coronary Artery Disease

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2023 Dec 14

PMID 38097358

Authors

Wangmeng Zhang

Minmin Zhao

Li Xin

Ximei Qi

Ping Cao

Jiyan Wang

Xin Li

Affiliations

Soon will be listed here.

Abstract

Coronary artery disease (CAD) is the most common aging-related disease in adults. We used bioinformatics analysis to study genes associated with aging in patients with CAD. The microarray data of the GSE12288 dataset were downloaded from the Gene Expression Omnibus database to obtain 934 CAD-associated differentially expressed genes. By overlaying them with aging-related genes in the Aging Atlas database, 33 differentially expressed aging-related genes (DEARGs) were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the 33 DEARGs were mainly enriched in cell adhesion and activation, Th17 and Th1/Th2 cell differentiation, and longevity regulation pathways. Hub genes were further screened using multiple algorithms of Cytoscape software and validation set GSE71226. Clinical samples were then collected, and the expression of hub genes in whole blood was detected by real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blot at the transcription and translation levels. Finally, and were identified as hub genes. The results of this study suggest that and are closely related to CAD. These findings provide a theoretical basis for the association between aging effectors and CAD, and indicate that these genes may be promising biomarkers for the diagnosis and treatment of CAD.

References

de Yebenes V, Briones A, Martos-Folgado I, Mur S, Oller J, Bilal F . Aging-Associated miR-217 Aggravates Atherosclerosis and Promotes Cardiovascular Dysfunction. Arterioscler Thromb Vasc Biol. 2020; 40(10):2408-2424. PMC: 7505150. DOI: 10.1161/ATVBAHA.120.314333. View

Li J, Huang K, Hu G, Babarinde I, Li Y, Dong X . An alternative CTCF isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis. Nat Commun. 2019; 10(1):1535. PMC: 6449404. DOI: 10.1038/s41467-019-08949-w. View

Divella R, Daniele A, De Luca R, Mazzocca A, Ruggieri E, Savino E . Synergism of Adipocytokine Profile and Polymorphisms in NAFLD-associated MetS Predict Colorectal Liver Metastases Outgrowth. Cancer Genomics Proteomics. 2019; 16(6):519-530. PMC: 6885361. DOI: 10.21873/cgp.20154. View

Wandrer F, Liebig S, Marhenke S, Vogel A, John K, Manns M . TNF-Receptor-1 inhibition reduces liver steatosis, hepatocellular injury and fibrosis in NAFLD mice. Cell Death Dis. 2020; 11(3):212. PMC: 7109108. DOI: 10.1038/s41419-020-2411-6. View

Huang G, Thatcher J, McAnally J, Kong Y, Qi X, Tan W . C/EBP transcription factors mediate epicardial activation during heart development and injury. Science. 2012; 338(6114):1599-603. PMC: 3613149. DOI: 10.1126/science.1229765. View

Kanehisa M, Sato Y, Kawashima M, Furumichi M, Tanabe M . KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 2015; 44(D1):D457-62. PMC: 4702792. DOI: 10.1093/nar/gkv1070. View

He S, Wang D, Meng J, Cheng X, Bi Q, Zhong G . HSP90-Mediates Liraglutide Preconditioning-Induced Cardioprotection by Inhibiting C5a and NF-κB. J Invest Surg. 2021; 35(5):1012-1020. DOI: 10.1080/08941939.2021.1989729. View

Cheng R, Xu X, Yang S, Mi Z, Zhao Y, Gao J . The underlying molecular mechanisms and biomarkers of plaque vulnerability based on bioinformatics analysis. Eur J Med Res. 2022; 27(1):212. PMC: 9615401. DOI: 10.1186/s40001-022-00840-7. View

Trembinski D, Bink D, Theodorou K, Sommer J, Fischer A, van Bergen A . Aging-regulated anti-apoptotic long non-coding RNA Sarrah augments recovery from acute myocardial infarction. Nat Commun. 2020; 11(1):2039. PMC: 7184724. DOI: 10.1038/s41467-020-15995-2. View

10.

Bristol J, Morrison T, Kenney S . CCAAT/enhancer binding proteins alpha and beta regulate the tumor necrosis factor receptor 1 gene promoter. Mol Immunol. 2009; 46(13):2706-13. PMC: 2724677. DOI: 10.1016/j.molimm.2009.05.024. View

11.

Watanabe M, Inukai K, Katagiri H, Awata T, Oka Y, Katayama S . Regulation of PPAR gamma transcriptional activity in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2002; 300(2):429-36. DOI: 10.1016/s0006-291x(02)02860-7. View

12.

Zhong G, Tu R, Zeng Z, Li Q, Li S, He Y . Novel functional role of heat shock protein 90 in protein kinase C-mediated ischemic postconditioning. J Surg Res. 2014; 189(2):198-206. DOI: 10.1016/j.jss.2014.01.038. View

13.

Terzic A, Waldman S . Chronic diseases: the emerging pandemic. Clin Transl Sci. 2011; 4(3):225-6. PMC: 5439863. DOI: 10.1111/j.1752-8062.2011.00295.x. View

14.

Bullinger L . CEBPA mutations in AML: site matters. Blood. 2022; 139(1):6-7. DOI: 10.1182/blood.2021013557. View

15.

Waldman S, Terzic A . Cardiovascular health: the global challenge. Clin Pharmacol Ther. 2011; 90(4):483-5. DOI: 10.1038/clpt.2011.213. View

16.

Hadrich F, Sayadi S . Apigetrin inhibits adipogenesis in 3T3-L1 cells by downregulating PPARγ and CEBP-α. Lipids Health Dis. 2018; 17(1):95. PMC: 5922308. DOI: 10.1186/s12944-018-0738-0. View

17.

Lippi G, Favaloro E, Sanchis-Gomar F . Sudden Cardiac and Noncardiac Death in Sports: Epidemiology, Causes, Pathogenesis, and Prevention. Semin Thromb Hemost. 2018; 44(8):780-786. DOI: 10.1055/s-0038-1661334. View

18.

SCANLON P, Faxon D, Audet A, Carabello B, Dehmer G, Eagle K . ACC/AHA guidelines for coronary angiography. A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee on Coronary Angiography). Developed in collaboration with the Society for Cardiac.... J Am Coll Cardiol. 1999; 33(6):1756-824. DOI: 10.1016/s0735-1097(99)00126-6. View

19.

Zhang L, Zhou F, Yu X, Zhu Y, Zhou Y, Liu J . C/EBPα deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice. Cell Death Dis. 2019; 10(10):684. PMC: 6746733. DOI: 10.1038/s41419-019-1933-2. View

20.

Andujar-Vera F, Ferrer-Millan M, Garcia-Fontana C, Garcia-Fontana B, Gonzalez-Salvatierra S, Sanabria-de la Torre R . Analysis of the Genetic Relationship between Atherosclerosis and Non-Alcoholic Fatty Liver Disease through Biological Interaction Networks. Int J Mol Sci. 2023; 24(4). PMC: 9966194. DOI: 10.3390/ijms24044124. View