WGCNA and molecular docking identify hub genes for cardiac aging

Front Cardiovasc Med. 2023 Apr 27:10:1146225. doi: 10.3389/fcvm.2023.1146225. eCollection 2023.

Abstract

Background: Cardiac aging and ageing-related cardiovascular diseases remain increase medical and social burden. Discovering the molecular mechanisms associated with cardiac aging is expected to provide new perspectives for delaying aging and related disease treatment.

Methods: The samples in GEO database were divided into older group and younger group based on age. Age-associated differentially expressed genes (DEGs) were identified by limma package. Gene modules significantly associated with age were mined using weighted gene co-expression network analysis (WGCNA). Protein-protein interaction networks (PPI) networks were developed using genes within modules, and topological analysis on the networks was performed to identify hub genes in cardiac aging. Pearson correlation was used to analyze the association among hub genes and immune and immune-related pathways. Molecular docking of hub genes and the anti-aging drug Sirolimus was performed to explore the potential role of hub genes in treating cardiac aging.

Results: We found a generally negative correlation between age and immunity, with a significant negative correlation between age and b_cell_receptor_signaling_pathway, fc_gamma_r_mediated_phagocytosis, chemokine signaling pathway, t-cell receptor signaling pathway, toll_like_receptor_signaling_pathway, and jak_stat_signaling_pathway, respectively. Finally, 10 cardiac aging-related hub genes including LCP2, PTPRC, RAC2, CD48, CD68, CCR2, CCL2, IL10, CCL5 and IGF1 were identified. 10-hub genes were closely associated with age and immune-related pathways. There was a strong binding interaction between Sirolimus-CCR2. CCR2 may be a key target for Sirolimus in the treatment of cardiac aging.

Conclusion: The 10 hub genes may be potential therapeutic targets for cardiac aging, and our study provided new ideas for the treatment of cardiac aging.

Keywords: GEO; anti-aging; bioinformatics; cardiac aging; immunity.

Grants and funding

This work was supported by grants from the Natural Science Foundation of Hainan Province (821QN389, 821MS112, 822MS198, 820MS126, 820QN383), the Excellent Youth Incubation Program of Chinese People's Liberation Army General Hospital (2020-YQPY-007), the Military Medical Science and Technology Youth Incubation Program (20QNPY110, 19QNP060), the National Key R&D Program of China (2018YFC2000400), the National S&T Resource Sharing Service Platform Project of China (YCZYPT[2018]07), the Specific Research Fund of Innovation Platform for Academicians of Hainan Province (YSPTZX202216), the Medical Big Data R&D Project of Chinese People's Liberation Army General Hospital (MBD2018030), the China Postdoctoral Science Foundation Funded Project (2019M650359, 2020M682816, 2021T140298), the Heatstroke Treatment and Research Center of PLA (413EGZ1D10), the Simulation Training for Treatment of Heat Stroke, and the Major Science and Technology Programme of Hainan Province (ZDKJ2019012).