Rho kinase inhibitors: a novel therapeutical intervention in asthma?
In asthma, inflammatory mediators that are released in the airways by recruited inflammatory cells and by resident structural cells result in airway hyperresponsiveness caused by increased bronchoconstriction. In addition, chronic inflammation appears to drive remodelling of the airways that contributes to the development of fixed airway obstruction and airway hyperresponsiveness in chronic asthma. Airway remodelling includes several key features such as excessive deposition of extracellular matrix proteins in the airway wall (fibrosis) and increased abundance of contractile airway smooth muscle encircling the airways. Current asthma therapy fails to inhibit these features satisfactorily. This review focuses on Rho kinase as a potential drug target in asthma, as compelling evidence from animal models and ex vivo studies suggests a central role for this enzyme and its associated signalling in acute and chronic airway hyperresponsiveness.
Schaafsma
Dedmer
D
Department of Physiology & Internal Medicine, and Section of Respiratory Disease, University of Manitoba, Winnipeg, Manitoba, Canada. schaafsm@cc.umanitoba.ca
Gosens
Reinoud
R
Zaagsma
Johan
J
Halayko
Andrew J
AJ
Meurs
Herman
H
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology
D018927:Anti-Asthmatic Agents; D004791:Enzyme Inhibitors; D054460:rho-Associated Kinases