On Valve Interstitial Cell Signaling: The Link Between Multiscale Mechanics and Mechanobiology

Heart valves function in one of the most mechanically demanding environments in the body to ensure unidirectional blood flow. The resident valve interstitial cells respond to this mechanical environment and maintain the structure and integrity of the heart valve tissues to preserve homeostasis. While the mechanics of organ-tissue-cell heart valve function has progressed, the intracellular signaling network downstream of mechanical stimuli has not been fully elucidated. This has hindered efforts to both understand heart valve mechanobiology and rationally identify drug targets for treating valve disease. In the present work, we review the current literature on VIC mechanobiology and then propose mechanistic mathematical modeling of the mechanically-stimulated VIC signaling response to comprehend the coupling between VIC mechanobiology and valve mechanics.