Expression of transforming growth factor-beta1, -beta2 and -beta3 in normal and diseased canine mitral valves.
The 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-beta (TGF-beta), a cytokine involved in extracellular matrix (ECM) regulation and mesenchymal cell differentiation. The present study investigates immunohistochemically the expression of TGF-beta1, -beta2, -beta3 and smooth muscle alpha actin (alpha-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 alpha-SMA but VSC displayed variable expression of TGF-beta1 (10% of VSC labelled), TGF-beta2 (1-5% labelled) and TGF-beta3 (50% labelled). In mild CVD the affected atrialis contain activated and proliferating alpha-SMA-positive VSC, which strongly expressed TGF-beta1 and -beta3, but only 10% of these cells expressed TGF-beta2. In unaffected areas of the leaflet there was selective increase in expression of TGF-beta1 and -beta3. In advanced CVD the activated subendothelial VSC strongly expressed alpha-SMA, TGF-beta1 and -beta3. Inactive VSC within the centre of the nodules had much less labelling for TGF-beta1 and -beta3. TGF-beta1 labelling was strong within the ECM. These data suggest that TGF-beta 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-beta expression.
Aupperle
H
H
Institut für Veterinär-Pathologie, Veterinärmedizinische Fakultät, Universität Leipzig, Halle, Germany. aupperle@rz.uni-leipzig.de
März
I
I
Thielebein
J
J
Schoon
H-A
HA
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D004285:Dogs; D006349:Heart Valve Diseases / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D007150:Immunohistochemistry; D008943:Mitral Valve / Q000378:metabolism* / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D000199:Actins; D016212:Transforming Growth Factor beta