A Constitutive Modelling Outlook on Arterial (dys)function: Bridging the Gap with the Clinic

Abstract The compliant properties of arteries are pivotal to cardiovascular function and arise from the concerted work of a highly specialised wall microstructure comprising compliant elastin, progressively recruited, stiff collagen fibres, and contractile vascular smooth muscle cells (VSMCs). Ageing and disease disrupt this (micro)structure–function coupling. While conventional clinical vascular indices allow for characterising the functional consequences of vascular ageing, they provide limited mechanistic insight into the underlying microstructural remodelling processes. Using illustrative examples from our group’s previous work, this paper, which provides an overview of my Career Development Lecture at the ARTERY24 conference (Cardiff, UK), proposes constitutive modelling as a useful framework to bridge this gap by representing whole-artery mechanics as the superimposed contributions of key microstructural constituents. The first example illustrates the ability of constitutive models to provide a detailed microstructural interpretation of the temporal dynamics of age-related arterial stiffening. The second example disentangles the microstructural determinants of arterial viscoelasticity and highlights the usefulness of viscoelastic characterisation to unravel microstructural disease mechanisms. The third demonstrates the formulation of a multi-scale model of the tri-layered arterial wall to highlight the functional uniqueness of the ascending aorta as the principal determinant of windkessel function. Finally, this paper recognises the need for extensive biomechanical data for model parametrisation as the main limiting factor to the widespread adoption of constitutive modelling in clinical settings. It discusses mechanobiologically informed constraints and longitudinal, multi-bed acquisitions of arterial waveforms as potential strategies to aid model parametrisation with sparse in vivo data, which may pave the way for future use of constitutive modelling to inform clinical decision-making.