Matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and transforming growth factor-β (TGF-β) in advanced canine myxomatous mitral valve disease

•Valvular and myocardial MMP2, MMP14, TGF-β1, TGF-β2 and myocardial TIMP2 and TIMP3 mRNA expression were increased in advanced MMVD.•Plasma MMP9 was decreased in advanced MMVD.•All affected markers correlated to increased echocardiographic parameters.•Narrowed myocardial vessels were associated with increased myocardial MMP2, MMP14, TIMP2 and TIMP3 mRNA expression.•Degenerative processes in MMVD involve MMPs, TIMPs and TGF-βs in both the mitral valve and the myocardium.

This study investigated mitral valve and myocardial protein and gene expression of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs) and transforming growth factor-β (TGF-β) and plasma MMP and TGF-β concentrations in age-matched dog groups euthanized due to either advanced myxomatous mitral valve disease (MMVD) or other reasons. Furthermore, echocardiographic data and lumen/area ratio were correlated with tissue and plasma levels of MMPs, TIMPs and TGF-βs.Mitral valve and myocardial gene expression of MMP2, MMP14, TGF-β1 and TGF-β2 were increased and plasma MMP9 was decreased in advanced MMVD dogs. Myocardial gene expression of TIMP2 and TIMP3 were increased in advanced MMVD. All affected markers correlated to echocardiographic parameters. Significantly narrowed lumen/area ratio was associated with increased myocardial expression of MMP2, MMP14, TIMP2 and TIMP3. No differences in tissue protein expression were recorded.MMP2, MMP14, TIMP2, TIMP3, TGF-β1 and TGF-β2 appear to play a local role in the development of advanced MMVD.