Center for Animal Biotechnology  CAB : Allergy/Asthma : Vascular Remodeling
 
CENTRE FOR ANIMAL BIOTECHNOLOGY  

Vacular Remodeling in Asthma

Scope

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)

Research outline

The development of a sheep model for vascular remodeling in asthmatic airways

Ken Snibson (Lab Head), Joanne Van der Velden, Donna Barker,Garry Barcham, Emmanuel Koumoundouros

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.


Key publications

  • O’Reilly M, Hooper SB, Allison BJ, Flecknoe SJ, Snibson K, Harding R, Sozo F. Persistent bronchiolar remodeling following brief ventilation of the very immature ovine lung. Am J Physiol Lung Cell Mol Physiol 2009, 297(5):L992-L1001.
  • Snibson K, De Matteo*, R, Koumoundouros E, Thompson B, Harding R. Lung function in developing lambs: is it affected by preterm birth? Journal of Applied Physiology 2009 107(4):1083-1088.
  • Bischof RJ, Bourke JE, Hirst SJ, Meeusen ENT, Snibson KJ, Van Der Velden. Measurement and Impact of Remodeling in the Lung: Airway Neovascularization in Asthma J. Proc Am Thorac Soc 2009, 6(8):673-677.
  • E. Koumoundouros, E., Snibson, K. J. and Mareels I M Y. Oesophageal techniques for deriving the lung dynamics of quietly breathing sheep 2008; IEEE Eng Med Biol Soc 1 2435-
  • Scheerlinck J., Snibson K., Bowles V. B., and Sutton P. Biomedical applications of sheep models: From asthma to vaccines. Trends Biotechnol 26(5): 259-66 2008
  • K Snibson and Richard Harding. Postnatal growth rate but not mild preterm birth influences airway structure in adult sheep challenged with House Dust Mite. Ex lung Research, 34 (2) 2008
  • Maritz, G., Probyn, M., De Matteo, R., Snibson, K., Harding R. Lung parenchyma at maturity is influenced by postnatal growth but not by moderately preterm birth in sheep. Neonatology 93 (1) 28-35 2008
  • Lofthouse, S., and Snibson, K., Claims of current corticosteroid patents for treating asthma, Recent Patents on Inflammation & Allergy Drug Discovery, 1 146-150 2007
  • Snibson, K. J., McMurtrie, L. S., Bischof, R. J., Koumoundouros, E., Cock, M., Harding, R.: Altered airway responsiveness in adult sheep born prematurely: Effects of allergen exposure. Ex lung Research 32 (6) 215-228 2006
  • Koumoundouros, E., Bischof, R. J., Meeusen, E. N., Mareels, I, M., Snibson, K., J.: Chronic airway disease: Deteriorating pulmonary function in sheep associated with repeated challenges of house dust mite. Ex lung Research 32 (7) 321-330 2006
  • Snibson, K. J., Bischof, R. J., Slocombe, R. F., and Meeusen, E. N.: Airway remodeling and inflammation in sheep lungs after chronic airway challenge with house dust mite. Clin Exp Allergy 35: (2) 146-152, 2005

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