Fibrotic vs. Myxomatous Remodeling of Mitral Valves

Abstract

Heart valves respond to load patterns imposed during valve function by remodeling their microstructure and matrix components. When exposed to loading or geometry outside of its normal range, the valve will remodel. We performed mechanical testing and biochemical analysis of extracellular matrix to compare normal mitral valves with valves that had remodeled due to primary or secondary valve disease. One form of remodeling we found was a fibrotic change, characterized by disorganized collagen produced to withstand high tensile loads. This remodeling occurred in congestive heart failure, in which the mitral valves were significantly less extensible, stiffer, and less viscous than autopsy control valves. These material changes were accompanied by higher cell and collagen concentrations as well as less water. We found a different type of remodeling in myxomatous mitral valves, in which abnormally low tensile loading results in the accumulation of glycosaminoglycans (GAGs). Myxomatous valves were more extensible, less stiff and strong, and contained more water and the GAGs hyaluronan and chondroitin 6-sulfate than normal mitral valves. Thus, valves that experience higher tensile loads than normal exhibited fibrotic scarring and stiffening, while valves with reduced normal loading demonstrated a degenerative edematous change with high extensibility and low strength.