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

• Structural changes to the lung are known to be associated with chronic asthma. In addition to the well-described alterations to the airway wall, asthma is also associated with vascular modifications, although this aspect of remodeling is poorly understood. We therefore sought to evaluate the character and kinetics of vascular remodeling in response to chronic aeroallergen exposure. However, since many OVA-driven models used to investigate allergic airway disease do so in the absence of persistent airway inflammation, we chose instead to employ a protocol of chronic respiratory exposure to house dust mite extract (HDM), which has been shown to induce persistent airway inflammation consistent with that seen in human asthmatics. Mice were exposed to HDM intranasally for 7 or 20 consecutive weeks, and resolution of the inflammatory and remodeling response to allergen was investigated 4 weeks following 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 following 7 and/or 20 weeks of allergen exposure, but returned to baseline following allergen withdrawal. We conclude that respiratory HDM exposure induces not only airway remodeling, but also pulmonary vascular remodeling, and in accordance with airway remodeling, some components of these structural changes may be irreversible.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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