title: Passive stiffness of airway smooth muscle: the next target for improving airway distensibility and treatment for asthma?
abstract: Reduced airway distensibility due to increased airway stiffness is a characteristic of asthma. Airway stiffness is determined by the property and structural organization of the various elements of the airway wall, and is often divided into active and passive components. Active stiffness is thought to be associated with activation of muscle cells in the airway wall. This component of stiffness can be inhibited when active force produced by the muscle is abolished. Passive stiffness, on the other hand, is thought to stem from non-muscle component of the airway wall, especially the collagen/elastin fibrous network of the extracellular matrix within which the muscle cells are embedded. In this brief review, the notion that passive stiffness is exclusively extracellular in origin is challenged. Recent evidence suggests that a substantial portion of the passive stiffness of an in vitro preparation of tracheal smooth muscle is calcium sensitive and is regulated by Rho-kinase, although the underlying mechanism and the details of regulation for the development of this intracellular passive stiffness are still largely unknown. To reduce airway stiffness different lines of attack must be tailored to different components of the stiffness. The regulatable passive stiffness is distinct from the relatively permanent stiffness of the extracellular matrix and the stiffness associated with active muscle contraction. To improve airway distensibility during asthma exacerbation, a comprehensive approach to reduce overall airway stiffness should therefore include a strategy for targeting the regulatable passive stiffness.
authors: Department of Pathology and Laboratory Medicine, The James Hogg Research Centre/St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Rm. 166, Vancouver, BC V6Z 1Y6, Canada. chun.seow@hli.ubc.ca
authors: Chun Y
authors: CY
authors: Seow
mesh_terms: D000818:Animals; D001249:Asthma / Q000503:physiopathology* / Q000628:therapy; D002118:Calcium / Q000378:metabolism*; D005110:Extracellular Space; D006801:Humans; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology*; D014132:Trachea / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D054460:rho-Associated Kinases; D002118:Calcium