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Characterization of the extracellular matrix metabolism in normal mitral valves and chronic valve disease (CVD) (syn. Endocardiosis) in dogs

Morphology, immunohistochemistry and mRNA analyses
: Aupperle, H.; Thielebein, J.; Schubert, A.; März, I.

DeGiovine, V.M.:
Dogs : Biology, behavior, and health disorders
Hauppauge, N.Y: Nova Science Publishers, 2012 (Animal science, issues and professions)
ISBN: 978-1-61209-653-7
Book Article
Fraunhofer IZI ()

Chronic heart valve disease (CVD) in dogs and the mitral valve prolapse (MVP) in man have similar characteristics but some clinical and pathological differences have been noted. The pathogenesis of CVD in dogs is still unclear but alterations of the extracellular matrix (ECM), enzymatic imbalances and atypical differentiation of valvular stromal cells (VSC) are discussed. The present study characterized the composition and distribution of the ECM components, the expression patterns of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), and the expression of different isoforms of the transforming growth factor- (TGF-). This was performed in mitral valves (MV) of unaffected dogs, as well as in dogs suffering from abnormal mitral valves due to CVD. MVs of 85 dogs (normal (n=22); mild (n=26), moderate (n=21), severe (n=16) CVD) were investigated macroscopically, histologically (H.-E., picrosirius red) and immunohistochemically (collagen I, III, VI, laminin , fibronectin, MMP-2, -9, -14, TIMP-2, -3, TGF-1, -2, -3, actin). Samples from normal (n=15) or diseased (n=10) canine MVs were subject to real-time polymerase chain reaction (PCR) for quantification of mRNA encoding MMP-2, -9, -14 and TIMP-2, -3. In the normal MV, ECM components were expressed in a typical layered pattern. MMP-2, -9, -14, and TIMP-2 were detected in single VSC. TIMP-3 showed moderate intra- and extracellular expression. The mRNA encoding MMP-2, -9 and -14 and TIMP-3 was low. The VSC showed no expression of actin but displayed mild expression of TGF-1 and TGF-2 and moderate expression of TGF-3. Advanced CVD was characterized by myxomatous nodular lesions, displaying a marginal and a central region containing mainly collagen I, VI and fibronectin in the former and collagen I and III in the latter. Immunohistochemical labelling intensity of MMP-2 and MMP-9 decreased significantly. However, mRNA values encoding MMP-2 and -9 were not decreased. In contrast, immunohistochemical MMP-14, T