Sex differences in arterial stiffness in a rat model of type 1 diabetes

Individuals with type 1 diabetes (T1D) exhibit elevated arterial stiffness and are at a higher risk of developing cardiovascular disease, both of which are sex dependent. However, whether sex differentially affects aortic structure at macro-, micro-, and nano-levels, which represent evaluations of the aorta at multiple scales, remains poorly understood. Therefore, we investigated sex-based differences in arterial stiffness by assessing pulse wave velocity (PWV), extracellular matrix remodeling, and atomic force microscopy (AFM) based medial-layer biomechanics in the aorta of a rat model of T1D.

Male and female Sprague Dawley rats were injected intraperitoneally with streptozotocin (65 mg/kg) to induce T1D. After 4 weeks, arterial stiffness and vascular alterations were evaluated in aortas of both sexes across multiple levels. At the macro-level, in vivo arterial stiffness was measured using ultrasound-based PWV. At the micro-level, structural remodeling was evaluated by quantifying collagen and elastin content in the aortic extracellular matrix. At the nano-level, biomechanical properties were assessed using AFM to determine Young's modulus in the aortic tissue.

T1D increased in vivo PWV in both sexes, with significantly higher PWV in diabetic males compared to diabetic females. Structural analysis revealed that diabetic males exhibited higher collagen deposition than diabetic females, whereas the Young's modulus increased with diabetes but showed no differences associated with sex.

These findings suggest that sex differences in T1D-related arterial stiffness at the macro level are primarily associated with extracellular matrix remodeling rather than nanoscale vascular smooth muscle cell stiffness at this disease stage.