Multiscale Simulations of the Healthy and Calcific Human Aortic Valve

In the heart’s aortic valve, maintenance of a healthy state and transition to disease states are modulated by the cells in the valve. The cells found within the valve leaflets are valvular interstitial cells (VICs) and those found on the fluid-facing surfaces are endothelial cells (ECs). Both types of cell are known to respond to their mechanical state; that is, the stresses and deformations imposed on a cell by its surrounding environment. Here we present a set of simulations to examine these mechanical states of the cells as the valve goes through its opening and closing cycle. We have created models at each of the cell, tissue, and organ length scales and introduced a system of reference configurations to link the scales. Each simulation and the set of multiscale simulation are verified against experimental data. This multiscale simulation approach allows us to accurately predict the dynamic, three-dimensional mechanical state of cells throughout the valve.