Rolle der Matrix-Metalloproteinasen bei der Mitralklappeninsuffizienz: Assoziation zwischen der Expression von MMP-1, MMP-9, TIMP-1 und TIMP-2, dem Mitralinsuffizienzgrad und der Ätiologie
Nach heutigem Wissensstand ist der Pathomechanismus der Entstehung der Mitralklappeninsuffizienz - mit eventueller Ausnahme der Endokarditis - mit mehreren Unklarheiten verbunden. Während sich mehrere Studien mit der Rolle von MMPs für den Mitralklappenprolaps beschäftigt haben, blieb der Ätiologie-...
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Format: | Doctoral Thesis |
Language: | German |
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Philipps-Universität Marburg
2019
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Online Access: | PDF Full Text |
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According to current knowledge, the pathomechanism of the development of mitral valve insufficiency - with the possible exception of endocarditis - is associated with several ambiguities. While several studies have addressed the role of MMPs in mitral valve prolapse, the aetiology-independent association between MMPs and mitral regurgitation has been less well studied. The primary objective of this work was to analyze the role of matrix metalloproteinases and their inhibitors in mitral valve insufficiency. For this purpose, the expression of MMP-1, MMP- 9, TIMP-1 and TIMP-2 was examined by immunohistochemistry and their distribution was evaluated according to clinical, echocardiographic and histopathological findings. A clear correlation between the expression of MMPs and the degree of mitral valve insufficiency was found in the present study. There was an increased expression of MMPs in mild mitral regurgitation and a relatively weak expression in severe cases. Furthermore, the aetiology of mitral regurgitation was considered in the evaluation. There was a significant difference in the expression of matrix metalloproteinases in mitral valves with endocarditis as opposed to mitral valves with degenerative disease. Within the degenerative group no relevant difference was found between the subgroups myxoid and sclerosed valve. In summary, the present study has shown that the extracellular remodeling and thus the destruction of the valve in chronic mitral regurgitation is a dynamic process. The increased expression of MMPs and their inhibitors in first-degree insufficiency is an indication that the molecular changes precede the macroscopic and thus echocardiographically diagnosable changes. This opens new perspectives in the early diagnosis of mitral regurgitation and should be further explored in future studies.