The role of chronic allergic inflammation in driving pulmonary vascular remodeling

Abstract

Introduction: Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by vascular proliferation and remodeling of the vascular wall. The prevalence of PAH can be a comorbidity associated with severe allergen-induced asthma. Asthma and PAH share common pathological features such as chronic inflammation, smooth muscle contraction and proliferation, and increased deposition of extracellular matrix (ECM) components. In asthmatics, chronic exposure to allergens induces the activation of inflammatory cells and their mediators that may contribute to irreversible dysregulation of airway epithelium, fibrosis. The induction of inflammation following chronic allergen exposure is strongly correlated with alterations in airway wall thickness, but it not known whether it contributes similarly to alterations in the lung vasculature. Additional factors, such as EMT, a process whereby epithelial cells migrate from the airways and increase expression of mesenchymal markers, and ECM molecules may also be important during airway remodeling. Conversely, a similar mechanism, EndoMT is may be a potential contributor to pulmonary vascular remodeling in PAH. Method: This study aimed to identify whether allergic inflammation contributes to vascular remodeling. Allergic inflammation was induced in mice by intranasal administration of allergens for up to 10 weeks. In lung tissue sections, blood vessel (BV) wall thickness, and occurrence of EMT or EndoMT were evaluated using immunofluorescence imaging. Additionally, collagen deposition was assessed using histological staining of lung sections. Additionally, the role of allergen-induced inflammation on alterations of vascular remodeling was assessed by using mice deficient. We assessed whether inhibition of allergen-induced inflammation could alter vascular remodeling. Results: Following chronic exposure to allergens, we found an overall increased in blood vessel wall and ⍺SMA levels around pulmonary BV. Following allergens exposure, we observed an increased in the expression of mesenchymal markers around the airway epithelium, and a reduction in tight junction proteins. Moreover, the amount of ECM around pulmonary BV was altered during allergic inflammation. We also found that inhibition of allergen induced inflammation reduced accumulation of ⍺SMA around BV walls. Conclusions: The outcome of this research enhanced our understanding of allergic inflammation relating to pulmonary vascular remodeling, and perhaps inhibiting allergen-induced inflammation may show a useful therapeutic strategy to prevent remodeling in PAH.