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 dyslipidaemiaassociated atherosclerosis remains incompletely understood. Here, we present an integrative bioinformatic analysis to investigate age- and sexdependent 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 networklevel 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