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Induction of Vascular Remodeling in the Lung by Chronic House Dust Mite Exposure

¹ Department of Experimental Medical Science, Division of Vascular and Airway Research, Lund University, Lund, Sweden; ² Department of Pathology and Molecular Medicine, Division of Respiratory Diseases and Allergy, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada

Correspondence and requests for reprints should be addressed to Kristina Rydell-Törmänen, PhD, Department of Experimental Medical Science, Division of Vascular and Airway Research, BMC D12, S-221 84, Lund, Sweden. E-mail: Kristina.Rydell-Tormanen{at}med.lu.se

Structural changes to the lung are associated with chronic asthma. In addition to alterations to the airway wall, asthma is associated with vascular modifications, although this aspect of remodeling is poorly understood. We sought to evaluate the character and kinetics of vascular remodeling in response to chronic aeroallergen exposure. Because many ovalbumin-driven models used to investigate allergic airway disease do so in the absence of persistent airway inflammation, we used a protocol of chronic respiratory exposure to house dust mite extract (HDME), which has been shown to induce persistent airway inflammation consistent with that seen in humans with asthma. Mice were exposed to HDME intranasally for 7 or 20 consecutive weeks, and resolution of the inflammatory and remodeling response to allergen was investigated 4 weeks after the end of a 7-week exposure protocol. Measures of vascular remodeling, including total collagen deposition, procollagen I production, endothelial and smooth muscle cell proliferation, smooth muscle area, and presence of myofibroblasts, were investigated histologically in lung vessels of different sizes and locations. We observed an increase in total collagen content, which did not resolve upon cessation of allergen exposure. Other parameters were significantly increased after 7 and/or 20 weeks of allergen exposure but returned to baseline after allergen withdrawal. We conclude that respiratory HDME exposure induces airway remodeling and pulmonary vascular remodeling, and, in accordance with airway remodeling, some components of these structural changes may be irreversible.

Key Words: vascular remodeling • house dust mite • smooth muscle • procollagen I • myofibroblast

CLINICAL RELEVANCE Vascular remodeling in asthma is poorly understood. We aimed to identify the nature of remodeling in different vessel types in a model of persistent allergic airway inflammation, and to determine whether these changes are reversible.