Sex differences in arterial remodelling among elderly patients with coronary artery disease

Background/Introduction Coronary artery disease (CAD) is highly prevalent among elderly patients and often requires revascularisation through coronary artery bypass grafting (CABG). Women undergoing CABG tend to present at older ages and experience higher 30-day mortality and graft failure rates than men, disparities that persist even after adjustment for clinical variables. Whether sex-specific structural and molecular differences in arterial grafts within the elderly population contribute to these disparate outcomes remains poorly understood. Purpose This study investigated sex-specific structural and molecular patterns of arterial remodelling in elderly patients with CAD undergoing CABG, aiming to elucidate the underlying biological differences between men and women within this high-risk age group. Methods Internal thoracic artery (ITA) specimens and clinical data were obtained from 88 elderly patients (59 males and 29 females; ≥65 years) undergoing elective CABG at our institutional vascular tissue biobank between July 2022 and August 2023. Histopathological evaluation was performed to assess structural remodelling and collagen architecture. Whole-transcriptome sequencing followed by pathway analyses using Ingenuity Pathway Analysis (IPA) and Gene Set Enrichment Analysis (GSEA) was conducted. Selected hub genes were further examined using quantitative real-time polymerase chain reaction (qRT-PCR). Results Elderly men and women exhibited distinct arterial remodelling patterns. Whilst intimal thickness was comparable between sexes, women showed a significantly thinner medial layer and higher intima-to-media ratio than men (P = 0.0154). Sex-related variations in collagen architecture were also observed. WTS identified 251 differentially expressed genes between men and women. In men, gene expression was enriched for epithelial–mesenchymal transition and extracellular matrix (ECM) structural constituents, with IPA indicating activation of vaso-occlusive and atherosclerosis signatures alongside downregulation of immune-regulatory pathways (Z = 1.528, P <0.001). In contrast, women showed enrichment of stress-response pathways including TNFα/NF-κB and p53 signalling, with significant downregulation of connective tissue integrity (Z = –2.008, P <0.001). qRT-PCR confirmed higher expression of ECM-related genes (ECM1, FN1) in men and upregulation of stress-response genes (JUN, JUNB, ATF3) in women (P <0.05). Conclusions Within the elderly population, men and women with CAD exhibit distinct arterial remodelling patterns, with differences in extracellular matrix-related and stress-response pathways. These findings provide biological insight into sex-associated differences in arterial graft remodelling in elderly patients undergoing CABG.