title: Expression of transforming growth factor-beta1, -beta2 and -beta3 in normal and diseased canine mitral valves.
abstract: 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.
authors.affiliation: Institut für Veterinär-Pathologie, Veterinärmedizinische Fakultät, Universität Leipzig, Halle, Germany. aupperle@rz.uni-leipzig.de
authors.forename: H
authors.initials: H
authors.lastname: Aupperle
authors.forename: I
authors.initials: I
authors.lastname: März
authors.forename: J
authors.initials: J
authors.lastname: Thielebein
authors.forename: H-A
authors.initials: HA
authors.lastname: Schoon
mesh_terms: 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*
chemical_list: D000199:Actins; D016212:Transforming Growth Factor beta