Angiogenic regulatory influence of extracellular matrix deposited by resting state asthmatic and non-asthmatic airway smooth muscle cells is similar.

Alen Faiz,Gavin Tjin,Alan James,Victor Bernal,Louise M Harkness,John G Elliot,Peter Horvatovich,Janette K Burgess,Anthony W Ashton

doi:10.1111/jcmm.16648

Abstract

The extracellular matrix (ECM) is the tissue microenvironment that regulates the characteristics of stromal and systemic cells to control processes such as inflammation and angiogenesis. Despite ongoing anti‐inflammatory treatment, low levels of inflammation exist in the airways in asthma, which alters ECM deposition by airway smooth muscle (ASM) cells. The altered ECM causes aberrant behaviour of cells, such as endothelial cells, in the airway tissue. We therefore sought to characterize the composition and angiogenic potential of the ECM deposited by asthmatic and non‐asthmatic ASM. After 72 hours under non‐stimulated conditions, the ECM deposited by primary human asthmatic ASM cells was equal in total protein, collagen I, III and fibronectin content to that from non‐asthmatic ASM cells. Further, the matrices of non‐asthmatic and asthmatic ASM cells were equivalent in regulating the growth, activity, attachment and migration of primary human umbilical vein endothelial cells (HUVECs). Under basal conditions, asthmatic and non‐asthmatic ASM cells intrinsically deposit an ECM of equivalent composition and angiogenic potential. Previous findings indicate that dysregulation of the airway ECM is driven even by low levels of inflammatory provocation. This study suggests the need for more effective anti‐inflammatory therapies in asthma to maintain the airway ECM and regulate ECM‐mediated aberrant angiogenesis.

Highlights

The underlying pathophysiology of asthma includes chronic airway inflammation, reversible obstruction, hypersensitive bronchial constriction and altered vascularization of the airway wall.[1]
Under non-stimulatory conditions asthmatic airway smooth muscle (ASM) cells deposit an extracellular matrix (ECM) which is similar in composition and functionality to that deposited by non-asthmatic ASM cells
These data, in light of the current literature, suggest the asthmatic ASM cells may be depositing an irregular ECM in response to the stimulatory conditions of the inflamed airway, and highlight the interplay between airway inflammation and airway remodelling in asthma

Summary

Introduction

The underlying pathophysiology of asthma includes chronic airway inflammation, reversible obstruction, hypersensitive bronchial constriction and altered vascularization of the airway wall.[1]. The airways of patients with asthma have alterations in the composition and functionality of the ECM.10-12 As a bioactive network of proteins, the ECM is vital for tissue structure and integrity[13] and is the microenvironment which regulates cell growth, metabolism, attachment and movement.[14,15] The ECM deposited by ASM cells contributes to the protein microenvironment of the muscle bundles, sub-epithelial space and adventitia. There have been no studies exploring the angiogenic potential of the asthmatic airway ECM. It is unclear what the exact nature of the composition and functionality of the ECM deposited by asthmatic ASM cells would be under non-stimulatory conditions and whether abnormal ECM deposition is an intrinsic feature of asthmatic ASM

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Conclusion