Multi-scale Modeling of the Heart Valve Interstitial Cell

Heart valve interstitial cells (VIC) are fibroblast-like cells that reside within the interstitium of heart valve leaflets. The biosynthetic activity of VICs is highly dependent upon the the mechanical demands of the extracellular environment. Thus, regular deformation of the leaflets throughout the cardiac cycle provides the mechanical stimulation that is necessary for VICs to maintain homeostasis of the valve and manage normal turnover of extracellular matrix constituents. When the deformation pattern of the VICs is altered during periods of growth or disease, VICs can undergo cellular activation and remodel the ECM of the valve to re-establish homeostasis. In order to better engineer treatments for heart valve diseases, it is of great importance to delineate the underlying mechanisms governing this crucial remodeling process. In this chapter, we present current experimental and computational modeling approaches used to study the complex multi-scale mechanical relationship between the valve leaflets and the underlying VICs. In addition, we discuss future directions toward modeling VIC signaling pathways and developing improved 3D multi-scale models of VICs.