Linking Layer-Specific Mitral Valve Interstitial Cell Deformation to Biosynthetic Response: Implications for Mitral Valve Repair

Nearly 40,000 Americans undergo mitral valve (MV) repair each year. The mitral annulus, however, flattens and undergoes significant conformational changes after repair—increasing the level of stress on the leaflets and... [ view full abstract ]

Nearly 40,000 Americans undergo mitral valve (MV) repair each year. The mitral annulus, however, flattens and undergoes significant conformational changes after repair—increasing the level of stress on the leaflets and reducing the durability of the repair. Our aim is to elucidate the link between MV micromechanical environment and valve interstitial cell (VIC) response in a stress overload scenario that is indicative of surgical repair. Porcine MVs were isolated and mounted onto our custom-built load-sensing tissue strip bioreactor for a 48-hour cyclic tension treatment at 1.17 Hz (10, 20, and 30% along the circumferential direction). Collagen, elastin, and glycosaminoglycan content were quantified and the RT2 Profiler PCR Array was used to examine expression patterns of 84 genes involved in ECM regulation. Cell and tissue-level deformations and structure were quantified using established methods (i.e., transmission electron microscopy and small angle light scattering). Results from this study reveal an important link between MV micromechanics and MVIC biosynthetic response, primarily an increase in VIC activation and biosynthetic activity at NAR>3.5. At hyper-physiological strain levels (>20%), VICs begin to express alpha smooth muscle actin, an indication of their transition into the myofibroblast phenotype and an increased secretion of collagen and sulfated glycosaminoglycans. This study provides important insights into the micromechanics of surgically repaired MVs by identifying cellular deformation as a potential mechanical basis for surgical repair failure. Future work will focus on designing a more physiologically realistic bioreactor that imposes biaxial deformation modes on the valve tissue to better emulate in vivo deformations.