Vacular Remodeling in Asthma
The aim of this program is to establish a physiologically relevant large animal model to investigate the cellular and molecular aspects of blood vessel changes in the airways of asthmatics.
Vascular remodeling in sheep model of chronic asthma. The figure shows collagen IV immunoreactivity in hematoxylin-counterstained histological sections showing increased airway vascularity in sheep exposed to repeated segmental allergen challenges of house dust mite. (A) A representative section of a non exposed control airway compared to (B) a section exposed to repeated segmental allergen challenges. Arrows indicate blood vessels in the lamina propria and in the outer airway walls. (adapted from Proceedings Of The American Thoracic Society Vol 6 2009, Joanne Van der Velden PhD data)
The development of a sheep model for vascular remodeling in asthmatic airways
It has become increasingly recognised that the bronchial mucosa is more vascularised in asthmatic patients than in healthy subjects. In asthmatics, the bronchial microcirculation can develop a number of qualitative and quantitative changes such as vasodilatation, increased permeability and angiogenesis. A number of studies have shown increases in size and number of bronchial blood vessels with angiogenic sprouts, known as neovascularisation, in asthmatic airways.
The increased number and/or dimensions of capillaries in the bronchial mucosa can contribute to airway lumen narrowing leading to airflow obstruction in asthma. These effects would occur in conjunction with the airway constriction effects due to airway smooth muscle (ASM) contraction during episodes of asthma. In addition to airflow limitation, a more vascularised bronchial mucosa has the obvious effects of allowing increased local bloodflow which acts as a conduit for increased traffic of inflammatory cells, inflammatory cytokines and mediators into the affected airways. Overall, highly vascularised and inflamed airways in chronic asthmatics leads to congestion and poor lung function outcomes.
We have developed a chronic asthma model using sheep to examine remodeling of lung tissues during persistent allergic inflammation. New data from our laboratory show that the airway walls become more vascularised in sheep exposed to repeated challenges of House Dust Mite (HDM). Thus, the sheep model we have developed is well placed to investigate the underlying mechanisms associated with the development of vascular remodeling in the airway walls of asthma.
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