Störungen des Metabolismus der extrazellularmatrix des Herzens bei der kaninen idiopathischen dilatativen Kardiomyopathie

While the pathogenesis of canine idiopathic dilative carchomyopathy (DCM) remains unclear, alterations of the composition and metabolism of the extracellularmatrix (ECM) are suspected to be involved. The normal hearts of 16 dogs and the hearts from 12 dogs with primary DCM were investigated grossly and histopathologically (H-E and pircrosirius red stain). The expression patterns of elastin, MMP-2, -9, -14 and of TIMP-2 and TIMP-3 were investigated immunohistochemically. Realtime PCR was used to measure the mRNA levels of MMP-2, MMP-9, TIMP-2 and TIMP-3. Histopathologically the "attenuated wavy fibre type" (wType; n = 6) and the "fatty infiltration-degeneration type" (fType; n = 6) of DCM were diagnosed. In areas of the fType morphology, collagen III was increased, while elastin deposits were seen in regions with attenuated wavy cardiomyocytes. Immunohistochemistry showed a significant increase of MMP-9 and a decrease of MMP-14 expression intensity in the cardiomyocytes of the DCM group. The immunhistochemical findings did not vary between the two histopathological types of DCM. The percentage of TIMP-3 positive fibrocytes was significantly increased in the DCM groups compared to the healthy controls. The mRNA analyses revealed a significant increase of MMP-9 mRNA in the DCM group compared to the controls. The mRNA levels of MMP-2, TIMP-2 and TIMP-3 did not vary significantly. In conclusion, the present study showed an alteration of the extracellularmatrix composition and a selective dysregulation of MMPs and TIMPs in canine idiopathic DCM. The increased MMP-9 expression is probably a major factor in the pathogenesis Of primary DCM. The two histopathological types of DCM are not characterized by different MMP/TIMP expression patterns but show variations in ECM composition.