3D Contractile and Remodeling Behaviors of Functionally Normal and Prolapsed Human Mitral Valve Interstitial Cells

Mitral valve prolapse (MVP) can lead to heart failure, arrhythmia, and death. The only treatments available for MVP are replacement or repair; alternative therapies remain elusive due to lack of knowledge of the underlying pathological processes. The goal of the present study was thus to explore how MVP affects human mitral valve interstitial cell (hMVICs) extracellular matrix (ECM) remodeling and basal contractility characteristics. Isolated MVP and physiologically normal hMVICs were embedded in poly(ethylene) glycol-based hydrogels containing fluorescent fiducial markers and 3D traction force microscopy via inverse modeling was employed to determine the local change in hMVIC hydrogels due to enzymatic degradation and collagen deposition. Results indicated pronounced hydrogel softening occurred generally further from the hMVICs, whereas stiffening occurred in close proximity to hMVICs due to collagen deposition as verified by collagen-staining. MVP hMVICs induced greater hydrogel stiffening and less degradation than normal hMVICs. Interestingly, even though MVP hMVICs had higher basal contractile displacements, their corresponding traction forces and hydrogel strain energy densities were significantly lower than those of normal hMVICs. These findings elucidate, for the first time, that MVP hMVICs have significantly altered biophysical contractile and ECM remodeling behaviors compared to normal hMVICs.