Abstract
Objective: Advancing age is a major risk factor of atherosclerosis (AS). Nevertheless, the mechanism underlying this phenomenon remains indistinct. Herein, this study conducted a comprehensive analysis of the biological implications of aging-related genes in AS. Methods: Gene expression profiles of AS and non-AS samples were curated from the GEO project. Differential expression analysis was adopted for screening AS-specific aging-related genes. LASSO regression analysis was presented for constructing a diagnostic model, and the discriminatory capacity was evaluated with ROC curves. Through consensus clustering analysis, aging-based molecular subtypes were conducted. Immune levels were estimated based on the expression of HLAs, immune checkpoints, and immune cell infiltrations. Key genes were then identified via WGCNA. The effects of CEBPB knockdown on macrophage polarization were examined with western blotting and ELISA. Furthermore, macrophages were exposed to 100 mg/L ox-LDL for 48 h to induce macrophage foam cells. After silencing CEBPB, markers of cholesterol uptake, esterification and hydrolysis, and efflux were detected with western blotting. Results: This study identified 28 AS-specific aging-related genes. The aging-related gene signature was developed, which could accurately diagnose AS in both the GSE20129 (AUC = 0.898) and GSE43292 (AUC = 0.685) datasets. Based on the expression profiling of AS-specific aging-related genes, two molecular subtypes were clustered, and with diverse immune infiltration features. The molecular subtype–relevant genes were obtained with WGCNA, which were markedly associated with immune activation. Silencing CEBPB triggered anti-inflammatory M2-like polarization and suppressed foam cell formation. Conclusion: Our findings suggest the critical implications of aging-related genes in diagnosing AS and modulating immune infiltrations.
Highlights
The number of elderly people is increasing globally, and cardiovascular diseases, especially atherosclerosis (AS), act as the biggest cause of morbidity and mortality among this population (Lorenzo et al, 2021)
The molecular subtype–relevant genes were obtained with weighted gene correlation network analysis (WGCNA), which were markedly associated with immune activation
Our findings suggest the critical implications of aging-related genes in diagnosing AS and modulating immune infiltrations
Summary
The number of elderly people (aged >65 years) is increasing globally, and cardiovascular diseases, especially atherosclerosis (AS), act as the biggest cause of morbidity and mortality among this population (Lorenzo et al, 2021). AS is the most common underlying pathology of coronary artery diseases, peripheral artery diseases, and cerebrovascular diseases (Wolf and Ley, 2019). It is an aging-related disorder that is in relation to long-term exposure to cardiovascular risk factors. Increasing age acts as an independent risk factor of AS progression (Wang and Bennett, 2012). The aging of the vascular system is a key determinant of the development of AS (de Yébenes et al, 2020). Indepth knowledge is required to fully uncover aging-related genes, to expound aging and AS intertwining, which allows us to develop more effective therapeutic strategies, and to decrease the burden of AS
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
