Smooth muscle molecular mechanics in airway hyperresponsiveness and asthma.
Asthma is a respiratory disorder characterized by airway inflammation and hyperresponsiveness associated with reversible airway obstruction. The relative contributions of airway hyperresponsiveness and inflammation are still debated, but ultimately, airway narrowing mediated by airway smooth muscle contraction is the final pathway to asthma. Considerable effort has been devoted towards identifying the factors that lead to the airway smooth muscle hypercontractility observed in asthma, and this will be the focus of this review. Airway remodeling has been observed in severe and fatal asthma. However, it is unclear whether remodeling plays a protective role or worsens airway responsiveness. Smooth muscle plasticity is a mechanism likely implicated in asthma, whereby contractile filament rearrangements lead to maximal force production, independent of muscle length. Increased smooth muscle rate of shortening via altered signaling pathways or altered contractile protein expression has been demonstrated in asthma and in numerous models of airway hyperresponsiveness. Increased rate of shortening is implicated in counteracting the relaxing effect of tidal breathing and deep inspirations, thereby creating a contracted airway smooth muscle steady-state. Further studies are therefore required to understand the numerous mechanisms leading to the airway hyperresponsiveness observed in asthma as well as their multiple interactions.
Gil
Fulvio R
FR
Meakins-Christie Laboratories, McGill University, 3626 St-Urbain Street, Montréal, QC H2X 2P2, Canada.
Lauzon
Anne-Marie
AM
D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism* / Q000503:physiopathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D024745:Smooth Muscle Myosins / Q000378:metabolism*
D018994:Myosin Light Chains; D009219:Myosin-Light-Chain Kinase; D043263:Myosin-Light-Chain Phosphatase; D024745:Smooth Muscle Myosins; D018995:Myosin Heavy Chains