Evidence for Interstitial Cell-Driven Restoration of Homeostasis in Heart Valve Remodeling

The mitral valve (MV) is an integral part of the left ventricle (LV), connected via the papillary muscles and annulus. Changes to the geometry or contractile motion of the LV (e.g. due to infarction) thus affect the external... [ view full abstract ]

The mitral valve (MV) is an integral part of the left ventricle (LV), connected via the papillary muscles and annulus. Changes to the geometry or contractile motion of the LV (e.g. due to infarction) thus affect the external boundary conditions of the MV, which in turn place the MV leaflets in a state of altered strain. In response to this, the MV undergoes a complex process of growth and remodeling (G&R) to adapt to its new ventricular environment. Pregnancy represents a non-pathological LV volume overload paradigm for increased MV loading, and has been shown to produce rapid, dramatic changes in the mechanical behavior and structure of MV leaflet tissue. In the present study, we used a structural constitutive modeling approach to elucidate the mechanisms through which changes in tissue composition and collagen fiber architecture can produce adaptive changes in the mechanical properties of the MV anterior leaflet during pregnancy-induced overload. We found that the onset and structural effects of G&R (figure, a and b) were associated with a biphasic change in the average nuclear aspect ratio of MV interstitial cells (figure, c). Our results together suggest that MV G&R is actively mediated at the cell level to restore homeostatic patterns of tissue and cellular deformation by way of the continual structural changes we have uncovered. This finding has significant implications in efforts to understand and predict MV G&R following myocardial infarction and MV surgical repair (e.g. annuloplasty), both of which place the valve under similar altered boundary conditions.