Multiscale biomechanics and mechanobiology of the tricuspid valve leaflets

Abstract

The tricuspid valve (TV) ensures adequate blood flow from the right atrium to the right ventricle. Proper TV competence relies on a structurally sound extra cellular matrix (ECM), having collagen and elastin as its primary constituents. However, Marfan syndrome, as a genetic disorder inhibiting elastin fibers, presents serious consequences primarily in the cardiovascular domain. An objective of this dissertation was to elucidate the impact that degraded elastin has on the mechanical response of the TV leaflets. Such mechanical changes may play a negative role in TV competence and inhibit its normal function. In particular, the loss of valvular competence is propitious to tricuspid regurgitation, a diseased condition where blood flows back in the atrium. Moreover, valve interstitial cells (VICs), residing in the valvular ECM, play a vital role in the maintenance and remodeling of the matrix. Through mechanotransduction, the VICs respond to environmental cues and stimuli. In the absence of elastin, as seen in Marfan syndrome, the ECM undergoes a micro-scale transformation. Another objective of this dissertation was to identify the role that native elastin plays at a cellular level by characterizing the nuclear aspect ratio of VICs as a function of the mechanical loading. The outcomes of this study has the potential to pave the way for further research in TV biomechanics and mechanobiology ultimately providing guidance in surgical approaches in TV disease management.--Author's abstract