Sex-dependent differences in central artery haemodynamics in normal and fibulin-5 deficient mice: implications for ageing

Abstract

Mouse models provide unique opportunities to study vascular disease, but they demand increased experimental and computational resolution. We describe a workflow for combining in vivo and in vitro biomechanical data to build mouse-specific computational models of the central vasculature including regional variations in biaxial wall stiffness, thickness and perivascular support. These fluid–solid interaction models are informed by micro-computed tomography imaging and in vivo ultrasound and pressure measurements, and include mouse-specific inflow and outflow boundary conditions. Hence, the model can capture three-dimensional unsteady flows and pulse wave characteristics. The utility of this experimental–computational approach is illustrated by comparing central artery biomechanics in adult wild-type and fibulin-5 deficient mice, a model of early vascular ageing. Findings are also examined as a function of sex. Computational results compare well with measurements and data available in the literature and suggest that pulse wave velocity, a spatially integrated measure of arterial stiffness, does not reflect well the presence of regional differences in stiffening, particularly those manifested in male versus female mice. Modelling results are also useful for comparing quantities that are difficult to measure or infer experimentally, including local pulse pressures at the renal arteries and characteristics of the peripheral vascular bed that may differ with disease.