From Airways to Arteries: Dissecting the Inflammatory Mechanisms of Pulmonary Vascular Remodeling in a Murine Model of Chronic Airway Inflammation
Year: 2026
Type: article
Abstract: 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.
Source: Biomedicines
Authors: Silvia Siragusa, Elena Tantillo, Silvia Parolo, Gloria Modafferi, Maria Laura Faietti, Giulia Natali, Paola Caruso, Sofia Beghi, Silvia Cantoni, Mary Delli Carpini, Maria Giulia Gualandri, Antonella Maria Nogara, Costanza Anna Maria Lagrasta, Vanessa Pitozzi, Maurizio Civelli, Gino Villetti, Enrico Domenici, Marcello Trevisani, Barbara Pioselli, Silvia Pontis
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,137
OpenAlex ID: W7164931052