MMP gene expression in dogs with isolated MR has confirmed that, at four months, there was down-regulation of a number of non-collagen genes important in ECM structure, down-regulation of pro-fibrotic connective tissue growth factor and plasminogen activator, and down-regulation of numerous genes in the TGF-β pathway.113 However, MMP-1 and MMP-9 gene expression was still markedly increased in these dogs with compensated MR compared with controls.113 As the LV started to dilate in dogs with chronic myxomatous mitral valve disease, MMP-9 levels decreased.129. Here, CCN2 is linked to miotic rate.