Age- and sex-dependent gene expression landscapes in dyslipidaemia-driven atherosclerosis

Ageing and biological sex are major determinants of cardiometabolic risk, yet their combined impact on the molecular regulation of dyslipidaemia-associated atherosclerosis remains incompletely understood. Here, we present an integrative bioinformatic analysis to investigate age- and sex-dependent gene expression patterns across tissues relevant to vascular disease. Using curated disease-gene associations from the T2DiACoD database, tissue-specific transcriptomic data from GTEx, and network-level information from STRING, we identify genes exhibiting monotonic age-related changes in basal expression in blood, tibial artery and aortic tissues. In tibial artery tissue, multiple genes involved in lipid metabolism, inflammatory signalling and vascular remodelling show age-associated expression changes, forming a connected protein-protein interaction network. Additional tissue-specific effects are observed for KLF14 in blood and TCF7L2 in aortic tissue. Sex-dependent expression differences are detected for a subset of age-modulated genes, highlighting the importance of incorporating sex as a biological variable. While exploratory, these findings suggest that ageing and sex shape coordinated transcriptional programmes in vascular tissues and provide candidate molecular signatures for further investigation into dyslipidaemia-related atherosclerosis.