Connecting Aortic Stiffness to Vascular Contraction: Does Sex Matter?

Abstract

This study was designed to connect aortic stiffness to vascular contraction in young male and female Wistar rats. We hypothesized that female animals display reduced intrinsic media-layer stiffness, which associates with improved vascular function. Atomic force microscopy (AFM)-based nanoindentation analysis was used to derive stiffness (Young’s modulus) in biaxially (i.e., longitudinal and circumferential) unloaded aortic rings. Reactivity studies compatible with uniaxial loading (i.e., circumferential) were used to assess vascular responses to a selective α1 adrenergic receptor agonist in the presence or absence of extracellular calcium. Elastin and collagen levels were indirectly evaluated with fluorescence microscopy and a picrosirius red staining kit, respectively. We report that male and female Wistar rats display similar AFM-derived aortic media-layer stiffness, even though female animals withstand higher aortic intima-media thickness-to-diameter ratio than males. Female animals also present reduced phenylephrine-induced aortic force development in concentration-response and time-force curves. Specifically, we observed impaired force displacement in both parts of the contraction curve (Aphasic and Atonic) in experiments conducted with and without extracellular calcium. Additionally, collagen levels were lower in female animals without significant elastin content and fragmentation changes. In summary, sex-related functional differences in isolated aortas appear to be related to dissimilarities in the dynamics of vascular reactivity and extracellular matrix composition rather than a direct response to a shift in intrinsic media-layer stiffness.

Investigating the relationship between residual stress and micromechanical properties of blood vessels using atomic force microscopy

“…This technique involves scanning imaging of tissues and cells, along with individual force measurements within predetermined ranges and frequencies. By capturing infrared light reflected from a cantilevered beam and converting the resulting displacement into an electrical signal through photoelectric conversion, AFM enables precise investigation of various samples (de Oliveira et al, 2022; Farniev et al, 2022; Grant & Twigg, 2013). AFM serves as an effective tool for examining tissue and cell morphology, as well as conducting individual force curve or force spectrum measurements within defined ranges and frequencies (Berquand et al, 2021).…”