title: Airway remodeling in asthma: new mechanisms and potential for pharmacological intervention.
abstract: The chronic inflammatory response within the airways of asthmatics is associated with structural changes termed airway remodeling. This remodeling process is a key feature of severe asthma. The 5-10% of patients with a severe form of the disease account for the higher morbidity and health costs related to asthma. Among the histopathological characteristics of airway remodeling, recent reports indicate that the increased mass of airway smooth muscle (ASM) plays a critical role. ASM cell proliferation in severe asthma implicates a gallopamil-sensitive calcium influx and the activation of calcium-calmodulin kinase IV leading to enhanced mitochondrial biogenesis through the activation of various transcription factors (PGC-1α, NRF-1 and mt-TFA). The altered expression and function of sarco/endoplasmic reticulum Ca(2+) pump could play a role in ASM remodeling in moderate to severe asthma. Additionally, aberrant communication between an injured airway epithelium and ASM could also contribute to disease severity. Airway remodeling is insensitive to corticosteroids and anti-leukotrienes whereas the effect of monoclonal antibodies (the anti-IgE omalizumab, the anti-interleukin-5 mepolizumab or anti-tumor necrosis factor-alpha) remains to be investigated. This review focuses on potential new therapeutic strategies targeting ASM cells, especially Ca(2+) and mitochondria-dependent pathways.
authors.affiliation: Université Bordeaux Segalen, LPCR, CIC 0005, F-33076 Bordeaux, France.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Girodet
authors.forename: Annaig
authors.initials: A
authors.lastname: Ozier
authors.forename: Imane
authors.initials: I
authors.lastname: Bara
authors.forename: Jose-Manuel
authors.initials: JM
authors.lastname: Tunon de Lara
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
authors.forename: Patrick
authors.initials: P
authors.lastname: Berger
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D002986:Clinical Trials as Topic / Q000639:trends; D006801:Humans
chemical_list: D018927:Anti-Asthmatic Agents; D000911:Antibodies, Monoclonal