Human Myxomatous Mitral Valves Exhibit Focal Expression of Cartilage-related Proteins - Human Myxomatous Mitral Valves Exhibit Focal Expression of Cartilage-related Proteins - Open Access Pub

Background: Heart valves share developmental signaling pathways with cartilage and bone. While calcific aortic valve disease (CAVD) has been associated with valve calcification and stenosis, suggestive of osteogenesis, myxomatous mitral valve disease (MMVD) is characterized by net matrix degradation, exuberant deposition of proteoglycan, and valve regurgitation. Methods: We determined the presence of cartilage-abundant proteoglycan, aggrecan; cartilage-specific type II collagen; chondrogenic transcription factor, Sox9; and osteogenic transcription factor, Runx2 in human normal and myxomatous mitral valve leaflets by immunohistochemistry. Results and Conclusions: Myxomatous, but not normal, mitral valves demonstrated sharp focal areas that were abundant in aggrecan, type II collagen, and Sox9. These focal areas co-localized with areas of myxomatous pathologic change on Movat staining. Some cells in these areas had a round and hypertrophic morphology reminiscent of chondrocytes. Runx2 was only weakly present in normal and myxomatous mitral valves. These findings suggest a focal pathologic process in MMVD that mimics chondrogenesis. DOI 10.14302/issn.2329-9487.jhc-12-102 The age-adjusted prevalence of valvular heart disease is estimated at 2.5% in the USA, and its prevalence increases sharply after 65 years of age due to the predominance of degenerative etiologies 1, 2. Degenerative valvular heart disease accounts for about 63% of native valvular heart disease. The most common manifestations of degenerative valvular disease are myxomatous mitral valve disease (MMVD) and calcific aortic valve disease (CAVD) 1. While both conditions are considered degenerative, MMVD and CAVD differ significantly in their functional manifestation and pathology. From a hemodynamic standpoint the most typical manifestation of MMVD is valve regurgitation, whereas the most common manifestation of CAVD is valve stenosis. Pathologically MMVD is characterized by gross leaflet thickening with chordae lengthening or rupture, net degradation of the extracellular matrix (ECM), and exuberant deposition of proteoglycan (PG)/glycosaminoglycan (GAG) 3, 4. On the other hand, CAVD is characterized by leaflet immobility, lipid accumulation, progressive leaflet fibrosis and calcification 5. The reasons for these divergent manifestations of valvular degeneration in the mitral and aortic valve are currently not understood. Research in heart valve development has suggested several commonalities between the pathways regulating this process and chondrogenesis, which in turn might have important