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1 Dept of Pathology, São Paulo University Medical School, São Paulo, Brazil, 2 West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, 5 School of Medicine and Pharmacology, University of Western Australia, Perth, Australia, 3 Dept of Vascular Surgery, Leiden University Medical Center, and 4 Division of Biomedical Research, TNO Prevention and Health, Leiden, The Netherlands.
CORRESPONDENCE: T. Mauad, Dept of Pathology, São Paulo University Medical School, Avenida Dr Arnaldo, 455, 01246-903, São Paulo SP, Brazil.. Fax: 55 1130628098. E-mail: tmauad{at}usp.br
Keywords: Airway smooth muscle, extracellular matrix, fatal asthma, metalloproteinases, remodelling, tissue inhibitor of metalloproteinase
Received: November 6, 2007
Accepted February 26, 2008
There is an intimate relationship between the extracellular matrix (ECM) and smooth muscle cells within the airways. Few studies have comprehensively assessed the composition of different ECM components and its regulators within the airway smooth muscle (ASM) in asthma.
With the aid of image analysis, the fractional areas of total collagen and elastic fibres were quantified within the ASM of 35 subjects with fatal asthma (FA) and compared with 10 nonfatal asthma (NFA) patients and 22 nonasthmatic control cases. Expression of collagen I and III, fibronectin, versican, matrix metalloproteinase (MMP)-1, -2, -9 and -12 and tissue inhibitor of metalloproteinase-1 and -2 was quantified within the ASM in 22 FA and 10 control cases.
In the large airways of FA cases, the fractional area of elastic fibres within the ASM was increased compared with NFA and controls. Similarly, fibronectin, MMP-9 and MMP-12 were increased within the ASM in large airways of FA cases compared with controls. Elastic fibres were increased in small airways in FA only in comparison with NFA cases.
There is altered extracellular matrix composition and a degradative environment within the airway smooth muscle in fatal asthma patients, which may have important consequences for the mechanical and synthetic functions of airway smooth muscle.
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