Distribution of myofibroblasts, smooth muscle-like cells, macrophages, and mast cells in mitral valve leaflets of dogs with myxomatous mitral valve disease

Objective - To map the cellular distribution and phenotypic alteration of the predominant stromal cell population throughout the entire valve length of dogs with myxomatous mitral valve disease (MMVD). Sample Population - 31 mitral valve complexes (ie, mitral valve leaflets) collected from 4 clinically normal dogs and 27 dogs with MMVD of varying severity. Procedures - A combination of standard histologic and immunohistochemical techniques was used to identify pathologic changes, the presence of mast cells, and the density and distribution of cells expressing vimentin, desmin, α-smooth muscle actin ((α-SMA), smooth muscle myosin, and the mocrophage marker MAC387 Results - Vimentin-positive cells predominated in the mitral valve leaflets from clinically normal dogs and were located throughout the leaflet, but cell density was appreciably decreased with disease progression, and minimal cell numbers were found in distinct myxomatous areas. Cells that were positive for α-SMA were uncommon in the mitral valve leaflets from clinically normal dogs and only seen in appreciable numbers in mitral valves of dogs with severe late-stage disease, in which cells were typically located close to the ventricularis valve surface. A slight increase in mast cell numbers was observed in the distal zone of affected leaflets. Conclusions and Clinical Relevance - Activated-myofibroblasts (α-SMA-positive cells) were increased and inactive-myofibroblasts (vimentin-positive cells) were reduced in mitral valve leaflets of dogs wit MMVD, compared with that of clinically normal dogs. Impact on Human Medicine - This is the first description of spatial and temporal alterations in mitral valve cells of any species with MMVD and has clinical importance in the understanding of disease development in dogs and humans.