title: Inhaled corticosteroids modulate the (+)insert smooth muscle myosin heavy chain in the equine asthmatic airways.
abstract: BACKGROUND
  Overexpression of the (+)insert smooth muscle myosin heavy chain (SMMHC) isoform could contribute to airway bronchospasm by increasing the velocity of contraction. Whether the (+)insert isoform is present in the small airways and its expression is reversible in asthma are unknown.
  
  
  OBJECTIVE
  To determine the anatomical location and the expression kinetics of the (+)insert SMMHC isoform in airways of horses with heaves and to evaluate its modulation in response to disease status.
  
  
  METHODS
  We evaluated the (+)insert SMMHC isoform in the airways of horses with heaves during disease exacerbation and remission, and in controls. The expression kinetics of the SMMHC (+)insert was then assessed at multiple time points in two studies: first, in horses with heaves treated for a 1-year period with antigen avoidance alone, inhaled corticosteroids alone or both; second, in horses with heaves before and after a 30-day natural antigen exposure. Gene expression analysis was assessed by quantitative PCR and protein expression was confirmed by targeted mass spectrometry.
  
  
  RESULTS
  The (+)insert SMMHC isoform was significantly increased in central and peripheral airways, but not in the trachea of heaves-affected horses in clinical exacerbation when compared horses with heaves in remission and controls. Both corticosteroid administration and antigen avoidance led to a significant reduction of the (+)insert expression in the airways. The (+)insert SMMHC isoform was not significantly increased in airways after 1 month of antigenic re-exposure.
  
  
  CONCLUSIONS
  The (+)insert SMMHC expression is increased throughout the bronchial tree in horses with heaves and reversible by corticosteroids administration and antigen avoidance.
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
authors.forename: Roxane
authors.initials: R
authors.lastname: Boivin
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
authors.forename: Amandine
authors.initials: A
authors.lastname: Vargas
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
authors.forename: Josiane
authors.initials: J
authors.lastname: Lefebvre-Lavoie
authors.affiliation: Meakins-Christie Laboratory, Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lauzon
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lavoie
mesh_terms: D000280:Administration, Inhalation; D000730:Androstadienes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000662:veterinary*; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005260:Female; D000068298:Fluticasone; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006734:Horse Diseases / Q000188:drug therapy / Q000378:metabolism*; D006736:Horses; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012074:Remission Induction; D024745:Smooth Muscle Myosins / Q000378:metabolism*; D014132:Trachea / Q000378:metabolism
chemical_list: D000730:Androstadienes; D000941:Antigens; D005938:Glucocorticoids; D020033:Protein Isoforms; D000068298:Fluticasone; D024745:Smooth Muscle Myosins; D018995:Myosin Heavy Chains
keywords: Asthma; Respiratory Muscles