Histomorphological findings and expression of matrix metalloproteinases and their tissue specific inhibitors (TIMPs) in normal tricuspid valves and in chronic tricuspid valvular disease in dogs

Abstract

The histomorphological findings and immunohistochemical expression of matrix metalloproteinases (MMPs-1, 2, 9 and 14) and their tissue inhibitors (TIMPs-2, 3 and 4) are reported in the parietal (pTV) and septal leaflets (sTV) of the tricuspid valves in normal dogs and dogs with chronic valvular disease (CVD). The layers of the normal sTV were not as well defined as in the pTV and the spongiosa of the sTV contained abundant mucopolysaccharides (MPS) and adipocytes. In CVD, there was expansion of the spongiosa of the pTV due to deposition of MPS, leading to formation of nodules along the free edge. In CVD, there was fibrosis of the atrialis of the sTV and formation of nodular deposits of MPS in the spongiosa and ventricularis, mainly affecting the proximal and middle parts of the leaflet. In dogs with normal pTV and sTV, MMPs-1 and 14 and TIMPs-2, 3 and 4 were expressed, while MMPs-2 and 9 were absent. In mild CVD, expression of MMPs-2, 9 and 14 were increased in the pTV, whereas small foci within the spongiosa contained MMP-9 and TIMP-3 positive cells. In advanced CVD, MMP-14 also was increased in the pTV. In mild CVD, there was increased expression of MMPs-1 and 2 and TIMP-2, but decreased expression of TIMP-4, in the sTV. Small foci with expression of MMP-14 and TIMPs-2, 3 and 4 were also present in the sTV in mild CVD. In advanced CVD, there was increased expression of MMPs-2 and 9 and TIMP-2 in the sTV. In CVD there is upregulation of various MMPs in the pTV, whereas there is a complex alteration in expression of MMPs and TIMPs in the sTV.