%0 Journal Article
%T Airway Smooth Muscle Hypercontractility in Asthma
%A Rachid Berair
%A Fay Hollins
%A Christopher Brightling
%J Journal of Allergy
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/185971
%X In recent years, asthma has been defined primarily as an inflammatory disorder with emphasis on inflammation being the principle underlying pathophysiological characteristic driving airway obstruction and remodelling. Morphological abnormalities of asthmatic airway smooth muscle (ASM), the primary structure responsible for airway obstruction seen in asthma, have long been described, but surprisingly, until recently, relatively small number of studies investigated whether asthmatic ASM was also fundamentally different in its functional properties. Evidence from recent studies done on single ASM cells and on ASM-impregnated gel cultures have shown that asthmatic ASM is intrinsically hypercontractile. Several elements of the ASM contraction apparatus in asthmatics and in animal models of asthma have been found to be different from nonasthmatics. These differences include some regulatory contractile proteins and also some components of both the calcium-dependent and calcium-independent contraction signalling pathways. Furthermore, oxidative stress was also found to be heightened in asthmatic ASM and contributes to hypercontractility. Understanding the abnormalities and mechanisms driving asthmatic ASM hypercontractility provides a great potential for the development of new targeted drugs, other than the conventional current anti-inflammatory and bronchodilator therapies, to address the desperate unmet need especially in patients with severe and persistent asthma. 1. Introduction Asthma is a chronic inflammatory disease characterized by variable airflow obstruction and bronchial hyperreactivity associated with airway remodelling [1]. Most of asthma symptoms result from airflow obstruction caused by airway lumen narrowing. Although this narrowing is multifactorial in origin, abnormalities of airway smooth muscle (ASM) structure and function have been identified as one of the main causes [2]. Increased ASM mass has long been recognized as a major component of airway remodelling [3, 4]. More recently, asthmatic ASM was also found to be abnormal in its functional properties with increasing evidence showing intrinsic heightened contractility independent of other structural cells and independent of the asthma inflammatory milieu. In this paper we will examine the evidence of ASM hypercontractility in asthmatics, explore the potential mechanisms driving it, discuss its relevance, and briefly suggest its role in future asthma therapy. 2. Evidence of ASM Hypercontractility in Asthmatics Abnormalities of asthmatic ASM structure and morphology have been described by
%U http://www.hindawi.com/journals/ja/2013/185971/