| Airway remodeling in asthma: New mechanisms and potential for pharmacological intervention. | |
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MedLine Citation:
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PMID: 21334378 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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-leucotrienes 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. |
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Authors:
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Pierre-Olivier Girodet; Annaig Ozier; Imane Bara; Jose-Manuel Tunon de Lara; Roger Marthan; Patrick Berger |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-2-17 |
Journal Detail:
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Title: Pharmacology & therapeutics Volume: - ISSN: 1879-016X ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-2-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7905840 Medline TA: Pharmacol Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2010. Published by Elsevier Inc. |
Affiliation:
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Université de Bordeaux, UB2, LPCR, CIC 0005, F-33076 Bordeaux, France; INSERM, U1045, CIC 0005, F-33076 Bordeaux, France; CHU de Bordeaux, Service d'Exploration Fonctionnelle Respiratoire, Service des Maladies Respiratoires, CIC 0005, F-33604 Pessac, France. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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