title: Asthma is not only an airway disease, but also a vascular disease.
abstract: Multiple studies have identified an expansion and morphological dysregulation of the bronchial vascular network in the airways of asthmatics. Increased number, size and density of blood vessels, as well as vascular leakage and plasma engorgement, have been reported in the airways of patients with all grades of asthma from mild to fatal. This neovascularisation is an increasingly commonly reported feature of airway remodelling; however, the pathophysiological impact of the increased vasculature in the bronchial wall and its significance to pulmonary function in asthma are unrecognised at this time. Multiple factors capable of influencing the development and persistence of the vascular network exist within asthmatic airway tissue. These include structural components of the altered extracellular matrix (ECM), imbalance of proteases and their endogenous inhibitors, release of active matrikines and the dysregulated levels of both soluble and matrix sequestered growth factors. This review will explore the features of the asthmatic airway which influence the development and persistence of the increased vascular network, as well as the effect of enhanced tissue perfusion on chronic inflammation and airway dynamics. The response of cells of the airways to the altered vascular profile and the subsequent influence on the features of airway remodelling will also be highlighted. We will explore the failure of current asthma therapeutics in "normalising" this vascular remodelling. Finally, we will summarize the outcomes of recent clinical trials which provide hope that anti-angiogenic therapies may be a potent asthma-resolving class of drugs and provide a new approach to asthma management in the future.
authors.affiliation: Respiratory Cellular and Molecular Biology, Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia; Discipline of Pharmacology, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Harkness
authors.affiliation: Division of Perinatal Research, Kolling Institute, Sydney, NSW, Australia.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Ashton
authors.affiliation: Respiratory Cellular and Molecular Biology, Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia; Discipline of Pharmacology, The University of Sydney, Sydney, NSW, Australia. Electronic address: janette.burgess@sydney.edu.au.
authors.forename: Janette K
authors.initials: JK
authors.lastname: Burgess
mesh_terms: D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D006801:Humans; D008168:Lung / Q000098:blood supply; D009389:Neovascularization, Pathologic; D014652:Vascular Diseases / Q000503:physiopathology*
keywords: Airway remodelling; Angiogenesis; Asthma; Neovascularisation