Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2438632 | Journal of Comparative Pathology | 2008 | 11 Pages |
SummaryThe pathogenesis of chronic valvular disease (CVD) in dogs remains unclear, but activation and proliferation of valvular stromal cells (VSC) and their transdifferentiation into myofibroblast-like cells has been described. These alterations may be influenced by transforming growth factor-β (TGF-β), a cytokine involved in extracellular matrix (ECM) regulation and mesenchymal cell differentiation. The present study investigates immunohistochemically the expression of TGF-β1, -β2, -β3 and smooth muscle alpha actin (α-SMA) in normal canine mitral valves (MVs) (n = 10) and in the valves of dogs with mild (n = 7), moderate (n = 14) and severe (n = 9) CVD. In normal mitral valves there was no expression of α-SMA but VSC displayed variable expression of TGF-β1 (10% of VSC labelled), TGF-β2 (1–5% labelled) and TGF-β3 (50% labelled). In mild CVD the affected atrialis contain activated and proliferating α-SMA-positive VSC, which strongly expressed TGF-β1 and -β3, but only 10% of these cells expressed TGF-β2. In unaffected areas of the leaflet there was selective increase in expression of TGF-β1 and -β3. In advanced CVD the activated subendothelial VSC strongly expressed α-SMA, TGF-β1 and -β3. Inactive VSC within the centre of the nodules had much less labelling for TGF-β1 and -β3. TGF-β1 labelling was strong within the ECM. These data suggest that TGF-β plays a role in the pathogenesis of CVD by inducing myofibroblast-like differentiation of VSC and ECM secretion. Changed haemodynamic forces and expression of matrix metalloproteinases (MMPs) may in turn regulate TGF-β expression.