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American journal of respiratory cell and molecular biology2015; 54(5); 718-727; doi: 10.1165/rcmb.2015-0180OC

Peripheral Airway Smooth Muscle, but Not the Trachealis, Is Hypercontractile in an Equine Model of Asthma.

Abstract: Heaves is a naturally occurring equine disease that shares many similarities with human asthma, including reversible antigen-induced bronchoconstriction, airway inflammation, and remodeling. The purpose of this study was to determine whether the trachealis muscle is mechanically representative of the peripheral airway smooth muscle (ASM) in an equine model of asthma. Tracheal and peripheral ASM of heaves-affected horses under exacerbation, or under clinical remission of the disease, and control horses were dissected and freed of epithelium to measure unloaded shortening velocity (Vmax), stress (force/cross-sectional area), methacholine effective concentration at which 50% of the maximum response is obtained, and stiffness. Myofibrillar Mg(2+)-ATPase activity, actomyosin in vitro motility, and contractile protein expression were also measured. Horses with heaves had significantly greater Vmax and Mg(2+)-ATPase activity in peripheral airway but not in tracheal smooth muscle. In addition, a significant correlation was found between Vmax and the time elapsed since the end of the corticosteroid treatment for the peripheral airways in horses with heaves. Maximal stress and stiffness were greater in the peripheral airways of the horses under remission compared with controls and the horses under exacerbation, potentially due to remodeling. Actomyosin in vitro motility was not different between controls and horses with heaves. These data demonstrate that peripheral ASM is mechanically and biochemically altered in heaves, whereas the trachealis behaves as in control horses. It is therefore conceivable that the trachealis muscle may not be representative of the peripheral ASM in human asthma either, but this will require further investigation.
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Publication Date: 2015-10-17 PubMed ID: 26473389PubMed Central: PMC4942195DOI: 10.1165/rcmb.2015-0180OCGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • N.I.H.
  • Extramural

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study investigates whether the trachealis muscle in horses suffering from “heaves,” a breathing condition similar to human asthma, behaves the same way as muscle in the peripheral airways. Results reveal that the muscle in the peripheral airways, but not the trachealis muscle, behaves differently in heaves-affected horses compared to healthy ones.

Objective of the Study

  • The aim of this research was to evaluate whether the trachealis muscle, the primary muscle of the trachea, is a reliable representative of the peripheral airway smooth muscle (ASM) in a horse model of asthma known as ‘heaves’.

Methodology

  • The researchers studied the tracheal and peripheral ASM of heaves-affected horses during flare-ups of the disease, during clinical remission, and of control horses.
  • The muscles were dissected and the epithelium removed to measure various parameters such as unloaded shortening velocity (Vmax), stress, the effective concentration of methacholine (a medication used to diagnose bronchial hyperreactivity) at which 50% maximum response is achieved, and stiffness.
  • Also measured were myofibrillar Mg(2+)-ATPase activity (an enzyme whose activity plays a key role in muscle contraction), actomyosin in vitro motility (the movement of actomyosin, a protein complex essential for muscle contraction) and the expression of contractile proteins.

Results

  • Horses with heaves exhibited significantly greater Vmax and Mg(2+)-ATPase activity in the peripheral airway but not in the tracheal smooth muscle.
  • A significant correlation was noted between Vmax and the time elapsed since the end of corticosteroid treatment for the peripheral airways in horses with heaves.
  • Maximal stress and stiffness were greater in the peripheral airways of the horses under remission compared to controls and the horses under exacerbation, suggesting potential remodeling of the airways due to repeated inflammation and healing.
  • No difference in actomyosin in vitro motility was observed between controls and horses with heaves.

Conclusion

  • The results of the study demonstrate that peripheral ASM is mechanically and biochemically altered in heaves, whereas the trachealis behaves as in control horses.
  • Thus, the study suggests that the trachealis muscle might not be a good representative of the peripheral ASM in human asthma, ALthough further research is needed to confirm this.

Cite This Article

APA
Matusovsky OS, Kachmar L, Ijpma G, Bates G, Zitouni N, Benedetti A, Lavoie JP, Lauzon AM. (2015). Peripheral Airway Smooth Muscle, but Not the Trachealis, Is Hypercontractile in an Equine Model of Asthma. Am J Respir Cell Mol Biol, 54(5), 718-727. https://doi.org/10.1165/rcmb.2015-0180OC

Publication

American journal of respiratory cell and molecular biology
ISSN: 1535-4989
NlmUniqueID: 8917225
Country: United States
Language: English
Volume: 54
Issue: 5
Pages: 718-727

Researcher Affiliations

Matusovsky, Oleg S
  • 1 Meakins-Christie Laboratories, McGill University, Research Institute of the McGill University Health Center, Montreal, Q, Canada.
Kachmar, Linda
  • 1 Meakins-Christie Laboratories, McGill University, Research Institute of the McGill University Health Center, Montreal, Q, Canada.
Ijpma, Gijs
  • 1 Meakins-Christie Laboratories, McGill University, Research Institute of the McGill University Health Center, Montreal, Q, Canada.
Bates, Genevieve
  • 1 Meakins-Christie Laboratories, McGill University, Research Institute of the McGill University Health Center, Montreal, Q, Canada.
Zitouni, Nedjma
  • 1 Meakins-Christie Laboratories, McGill University, Research Institute of the McGill University Health Center, Montreal, Q, Canada.
Benedetti, Andrea
  • 2 Department of Medicine, McGill University, Montreal, Q, Canada.
  • 3 Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, Montreal, Q, Canada.
  • 4 Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Q, Canada; and.
Lavoie, Jean-Pierre
  • 5 Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St.-Hyacinthe, Q, Canada.
Lauzon, Anne-Marie
  • 1 Meakins-Christie Laboratories, McGill University, Research Institute of the McGill University Health Center, Montreal, Q, Canada.
  • 2 Department of Medicine, McGill University, Montreal, Q, Canada.

MeSH Terms

  • Actin Cytoskeleton / metabolism
  • Animals
  • Asthma / physiopathology
  • Blotting, Western
  • Ca(2+) Mg(2+)-ATPase / metabolism
  • Contractile Proteins / metabolism
  • Disease Models, Animal
  • Female
  • Horse Diseases / physiopathology
  • Horses
  • Male
  • Methacholine Chloride
  • Muscle Contraction / physiology
  • Muscle, Smooth / physiopathology
  • Myofibrils / metabolism
  • Myosin Heavy Chains / metabolism
  • Myosins / metabolism
  • Respiratory Mechanics / physiology
  • Trachea / physiopathology

Grant Funding

  • R01 HL103405 / NHLBI NIH HHS
  • CIHR

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