A Proteomic Study Reveals the Relationship Between Arterial Stiffness and Hyperglycemia in Middle-Aged Obese Men

Objective: To investigate serum proteins and molecular pathways associated with arterial stiffness in middle-aged obese men. Methods: This cross-sectional analysis included 82 men aged 40–60 years with a BMI ≥ 25.0 kg/m 2 . Blood samples were collected for clinical and proteomic analyses, and arterial stiffness was measured using the cardio-ankle vascular index (CAVI). Participants were classified into arterial stiffness (n = 4), borderline (n = 13), and normal (n = 65) groups according to CAVI values. Results: Among the metabolic syndrome components, hyperglycemia was the only one that differed significantly across the CAVI groups. Comparative serum proteomic analysis between the arterial stiffness group and the normal and borderline groups identified 8,663 shared differentially expressed proteins (DEPs). Pathway enrichment analysis of these proteins identified the “Fluid shear stress and atherosclerosis” pathway as a significantly enriched pathway. Participants were subsequently classified into hyperglycemia and normoglycemia groups, and pathway analysis likewise identified “Fluid shear stress and atherosclerosis” as a significantly enriched pathway. Eighteen shared proteins were identified and implicated in antioxidant systems (NRF2, HO-1, GSTA1, GSTA3, GSTM1, and GSTM5), pro-atherogenic proteins (VCAM-1 and MMP-2), mechano-sensor proteins (ITGB3, SDC4, and ACVR1), and signaling proteins (AMPKα1, PI3K p85α, MEF2C, KLF2, RAC3, MKK6, and PIAS4). Conclusions: These findings provide preliminary evidence for a common molecular pathway linking arterial stiffness and hyperglycemia and identify candidate proteins for further investigation as potential biomarkers or therapeutic targets.