title: Effects of transforming growth factor-β3 and matrix metalloproteinase-3 on the pathogenesis of chronic mitral valvular disease in dogs.
abstract: OBJECTIVE
  To investigate the roles of transforming growth factor-β (TGF-β) isoforms and matrix metalloproteinases (MMPs) in development of chronic mitral valvular disease (CMVD) in dogs.
  
  
  METHODS
  12 mitral valve leaflets collected from cadavers of 5 clinically normal dogs and from 7 dogs with CMVD.
  
  
  METHODS
  Expression of TGF-β isoforms 1, 2, and 3; MMPs 1, 2, 3, and 9; TGF-β receptor II (TβR-II); and α smooth muscle actin (αSMA) in mitral valves of dogs with CMVD was compared with that in mitral valves from clinically normal dogs. Additionally, responses of valvular interstitial cells (VICs) to TGF-β3, MMP-3, and angiotensin-converting enzyme inhibitor (ACEI) as a suppressor of TGF-β3 were examined in vitro.
  
  
  RESULTS
  Expression of TGF-β3, TβR-II, αSMA, and MMP-3 was only detected in mitral valves of dogs with CMVD. Concentrations of αSMA and proteoglycans in cultured VICs were significantly increased following incubation with TGF-β3; treatment with MMP-3 resulted in increased amounts of active and total TGF-β3, and total TGF-β3 in VICs was significantly decreased by incubation with ACEI.
  
  
  CONCLUSIONS
  Findings suggested that increased TGF-β3 and MMP-3 contribute to the pathogenesis of valvular degeneration associated with CMVD. In addition, it is possible that the use of ACEI could effectively block pathological alterations in VICs associated with CMVD in vitro. Impact on Human Medicine-CMVD is associated with primary mitral valve prolapse and Marfan syndrome in humans. Results of the study reported here will help to elucidate the molecular mechanisms of CMVD in dogs and humans.
authors.affiliation: Department of Veterinary Internal Medicine, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo 180-8602, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Obayashi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyagawa-Tomita
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Koyama
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hirose
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004283:Dog Diseases / Q000209:etiology* / Q000378:metabolism; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006854:Hydrocortisone; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D008944:Mitral Valve Insufficiency / Q000378:metabolism / Q000662:veterinary*; D020033:Protein Isoforms; D053782:Transforming Growth Factor beta3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D053782:Transforming Growth Factor beta3; D019278:Matrix Metalloproteinase 3; D006854:Hydrocortisone