Ultrastructural morphologic evaluation of the phenotype of valvular interstitial cells in dogs with myxomatous degeneration of the mitral valve

Objective-To evaluate morphologic changes in valvular interstitial cells of dogs and to find evidence for disease-associated phenotypic changes in these cells. Animals-5 clinically normal dogs and 5 dogs with severe mitral valve endocardiosis. Procedure-Mitral valve leaflets were evaluated by use of transmission electron microscopy. Differences in cell type and cell location were identified. Results-A change in cell type toward a myofibroblast or smooth muscle cell phenotype was detected, with the smooth muscle cell type being most common. These cells had long amorphous cytoplasmic extensions, fibrillar cytoplasm, incomplete basal lamina, few mitochondria, and eccentrically placed nuclei but lacked smooth endoplasmic reticulum or Golgi complexes. Remaining valvular interstitial cells had heterochromatic nuclei and produced only minimal quantities of collagen. Compared with normal valves, myxomatous valves had many interstitial-like cells located adjacent to the endothelium. Deeper within the abnormal valves, cells with a heterogenous phenotype formed groupings that appeared to be anchored to adjacent collagen. Conclusions and Clinical Relevance-Myxomatous degeneration of the mitral valve in dogs is associated with phenotypic alteration, changing from an interstitial to a mixed myofibroblast or smooth muscle cell phenotype. A closer association between interstitial cells and the endoelium is evident in diseased valves. In response to the disease process, valvular interstitial cells of dogs appear to change toward a smooth muscle phenotype, possibly in an attempt to maintain valve tone and mechanical function.