Abstract
Purpose Mitral valve prolapse (MVP) can lead to heart failure, arrhythmia, and death. Current treatments for MVP are strictly surgical, while alternative therapies remain elusive due to lack of knowledge of underlying processes. Importantly, our understanding of cellular mechanisms of post-MVP repair remodeling that can lead to secondary surgery remain limited. We therefore explored how MVP affects human mitral valve interstitial cell (MVIC) extracellular matrix (ECM) remodeling and basal contractility. Methods Isolated MVP and physiologically normal MVICs were embedded in poly(ethylene) glycol-based hydrogels containing fluorescent microbeads (~ 1 μm) and imaged in the basal and deactivated states. 3D cell surface tractions and changes in MVIC hydrogel local moduli were then determined via inverse computational mechanics modeling. Results Hydrogel softening occurred further from MVIC surfaces, whereas pronounced stiffening occurred in close proximity, a result of collagen deposition as verified by collagen staining. MVP MVICs induced greater hydrogel stiffening and less degradation than normal MVICs. Interestingly, even though MVP MVICs had higher basal contractile displacements, their traction forces and hydrogel strain energy densities were significantly lower than those of normal MVICs. Conclusion These findings elucidate, for the first time, that MVP MVICs have significantly altered contractile and ECM remodeling behaviors compared to functionally normal MVICs. This result suggests that MVIC behaviors may affect how MVP responds to repair. Moreover, as our studies were performed on isolated MVICs, our observed differences in MVIC behaviors are intrinsic to MVIC phenotype and are not only due to the altered cellular microenvironment.