Myxomatous mitral valve disease is a frequent disorder that is most often diagnosed by echocardiography. It is characterized by moderate to severe regurgitation; prolapsed, voluminous leaflets; elongated chordae tendineae; and annular dilatation. The optimal surgical treatment is repair to remove the excess valve tissue, but concerns remain regarding the durability of the repair since the remaining tissue is diseased and likely mechanically compromised. Although histological studies have shown increased leaflet thickness, accumulation of glycosaminoglycans (GAGs), and focal disruption of collagen, myxoid leaflets and chordae have not been well quantified biochemially or biomechanically. It remains unclear whether leaflets prolapse and chordae rupture from intrinsic tissue weakness or from geometric valve abnormalities. Previous studies found that collagen and elastic fibers were disorganized and GAG concentration was increased. GAG content, however, was not examined across a wide range of ages or myxoid disease states. Because GAGs have diverse structural and regulatory roles that could lead to functional changes in connective tissues, this study proposes to identify different GAG types, structures, and quantities in normal and myxomatous mitral valves using innovative fluorophore-assisted carbohydrate electrophoresis (FACE) and immunohistochemical methods (Specific Aims 1a-b). These findings will then be correlated with mechanical properties (Specific Aim 1c) to determine if the cells in myxomatous and normal mitral valve organ cultures. In order to identify any phenotypic differences that would suggest a cell-mediated pathoetiology (Specific Aim 2). Ultimately, these results will be incorporated into a larger study and correlated with preoperative echocardiographic evaluations. Relating the biochemical and mechanical features of myxoid valves to clinical factors is important in properly selecting patients for mitral valve repair. The broad objective of this research, therefore, is to define the molecular nature of myxomatous degeneration so that surgical intervention can be better planned and managed.
