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This Article Full Text Full Text (PDF) All Versions of this Article: 287/6/L1165    most recent 00171.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Zheng, X. Articles by Bai, T. R Search for Related Content PubMed PubMed Citation Articles by Zheng, X. Articles by Bai, T. R

Cardiotrophin-1 alters airway smooth muscle structure and mechanical properties in airway explants

The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, St. Paul's Hospital, Vancouver, British Columbia, Canada V6Z 1Y6

Submitted 12 May 2004 ; accepted in final form 20 July 2004

Induction of hypertrophy and inhibition of apoptosis may be important mechanisms contributing to increased airway smooth muscle (ASM) mass in asthma. Data from our laboratory indicate that cardiotrophin-1 (CT-1) induces hypertrophy and inhibits apoptosis in isolated human ASM cells. To determine whether these novel effects of CT-1 also occur in the airway tissue milieu and to determine whether structural changes are accompanied by functional changes, matched pairs of guinea pig airway explants were treated with or without CT-1 for 7 days, and structural features as well as isometric and isotonic contractile and relaxant mechanical properties were measured. CT-1 (0.2–5 ng/ml) increased both myocyte mass and extracellular matrix in a concentration-dependent fashion. CT-1 (10 ng/ml)-treated tissues exhibited a significant increase in passive tension at all lengths on day 7; at optimal length, passive tension generated by CT-1-treated tissues was 1.72 ± 0.12 vs. 1.0 ± 0.1 g for control. Maximal isometric stress was decreased in the CT-1-treated group on day 7 (0.39 ± 0.10 kg/cm²) vs. control (0.77 ± 0.15 kg/cm², P < 0.05). Isoproterenol-induced relaxant potency was reduced in CT-1-treated tissues, log EC₅₀ being –7.28 ± 0.34 vs. –8.12 ± 0.25 M in control, P < 0.05. These data indicate that CT-1 alters ASM structural and mechanical properties in the tissue environment and suggest that structural changes found in the airway wall in asthma are not necessarily associated with increased responsiveness.

tracheal explants; mechanics; cytokines; asthma; matrix; smooth muscle hypertrophy

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