Introduction Mitral valve disease due to myxomatous degeneration causing mitral regurgitation (MR) and rheumatic fever causing stenosis (MS) are common forms of mitral valvular heart disease. The cellular mechanism causing the mitral valve abnormalities is not well known. We hypothesize that the mechanism of mitral valve degeneration is cellular proliferation and osteoblast mediated extracellular matrix production. To test this hypothesis we examined both degenerative and rheumatic human mitral valves replaced at surgery and compared them to normal human valves removed at cardiac transplantation. We examined immunohistochemistry, electron microscopy and microCT for osteoblast specific markers which are expressed during osteoblast cell differentiation.
Methods Degenerative mitral valves (N = 20), rheumatic mitral valves (N = 23) and control mitral valves (N = 20) were studied. Electron microscopy (EM) was performed for ultrastructural analysis of the valves. Immunohistochemistry was used to localize osteopontin, alpha actin, proliferating cell nuclear antigen and CD68. MicroCT and alizarin red (AR) demonstrated the amount of calcification. A 4-point grading system was used to visually describe the staining on each of the slides (1 = no staining, 4 = high staining).
Results The rheumatic calcified valves demonstrated a 4-fold increase in proliferation and bone matrix expression as compared to control and the degenerative mitral valves demonstrated a 2-fold increase in these markers. These results indicate that the degree of calcification correlates with the level of cellular proliferation which differ between the two different diseases. These markers were absent in the normal valves.
Conclusions These findings support the evidence that cellular proliferation and extracellular matrix production are important in the development of mitral valve disease. These conclusions provide the foundation for our understanding of the cellular processes important in the varying clinical presentations of mitral valve disease.
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