From Airways to Arteries: Dissecting the Inflammatory Mechanisms of Pulmonary Vascular Remodeling in a Murine Model of Chronic Airway Inflammation.

Background

Chronic Obstructive Pulmonary Disease (COPD) is a progressive, incurable condition marked by irreversible airflow limitation and systemic inflammation. Cardiovascular comorbidities, particularly pulmonary hypertension (PH), exacerbate disease severity. While cigarette smoke is a well-known trigger, non-smoking-related inflammatory pathways remain underexplored. This study investigates vascular remodeling in a murine model of inflammation induced by chronic exposure to house dust mite Farinae (HDM).

Methods

Female C57BL/6 mice were sensitized with HDM in Freund's Complete Adjuvant and challenged intranasally with HDM for six weeks. Lung inflammation, mucus hypersecretion, and vascular remodeling were evaluated via BAL, histology, immunofluorescence, echocardiography, gene expression, proteomics, and FlexiVent pulmonary function tests (FlexiVent system).

Results

HDM exposure induced a mixed inflammatory response, with elevated neutrophils, monocytes, and lymphocytes in BALF. Mucus hyperproduction (increase in MUC5AC/MUC5B) and impaired lung function (reduced FEV0.1/FVC) were observed. Vascular remodeling was evidenced by increased wall thickness, α-SMA expression, and collagen deposition. Proteomic analysis revealed dysregulation of endothelial markers and protease/antiprotease imbalance. HIF1-α was significantly upregulated in lung tissue and correlated with vascular and epithelial remodeling.

Conclusions

Chronic HDM exposure in mice recapitulates key features observed in subsets of COPD and PH, including inflammation-driven airway and vascular remodeling. HIF1-α emerges as a central regulator, linking hypoxia to structural changes. This model offers insights into the effect of non-smoking-related inflammatory pathways on bronchial and vascular remodeling that are potentially relevant for subgroups of COPD patients and highlights HIF1-α as a potential therapeutic target.