Extracellular matrix components and regulators within the airway smooth muscle in asthma

¹ Dept of Pathology, São Paulo University Medical School, São Paulo, Brazil
² West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, Australia;
³ Leiden University Medical Center, Department of Vascular Surgery Leiden, The Netherlands
⁴ TNO Prevention and Health, Division of Biomedical Research, Leiden, The Netherlands
⁵ West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, Australia;; and School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia

	Abstract

There is an intimate relationship between the extracellular matrix (ECM) and the smooth muscle (ASM) cells within the airways. Few studies have comprehensively assessed composition of different ECM components and its regulators within the ASM in asthma.

We quantified the fractional areas of total collagen and elastic fibers within the ASM of 35 subjects that died of asthma (FA) and compared them with 10 non-fatal asthma (NFA) and 22 non-asthmatic control cases. Collagen I and III, fibronectin, versican, matrix metalloproteinases (MMP)-1, -2, -9, -12 and their tissue inhibitors (TIMP)-1 and -2 expressions were quantified within the ASM in 22 FA and 10 control cases. Image analysis was used to quantitate ECM components as fractional areas of ASM.

In large airways of FA cases the fractional areas of elastic fibers was increased within the ASM compared with NFA and controls. Similarly, fibronectin, MMP-9 and MMP-12 within the ASM were increased in large airways of FA compared with controls. Elastic fibers were increased in FA compared with NFA only in small airways

There is an altered ECM composition and a degradative environment within the ASM in FA, which may have important consequences for ASM mechanical and synthetic functions.