Exposure to environmental pollution from iron ore pelletizing in pulmonary vascular remodeling of mice with elastase-induced lung inflammation: possible involvement of the cholinergic system

• Grant number: 25/14945-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2025
• End date: November 30, 2026
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Iolanda de Fátima Lopes Calvo Tibério
• Grantee: Felipe Rodrigues Paganini
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Environmental pollution is one of the main modifiable risk factors for chronic respiratory diseases such as Chronic Obstructive Pulmonary Disease (COPD). Among its sources, particulate matter (PM) derived from industrial activities like iron ore pelletizing plays a key role. Exposure to such pollutants is linked to persistent pulmonary inflammation and remodeling of both lung tissue and vasculature. Simultaneously, the cholinergic system - particularly acetylcholine (ACh) and its vesicular transporter (VAChT) - has emerged as a significant modulator of lung inflammation. VAChT deficiency reduces ACh release, exacerbating inflammatory responses and lung damage, as shown in experimental models.This project aims to investigate the effects of environmental exposure to iron-rich PM on pulmonary vascular remodeling in mice with elastase-induced lung inflammation and reduced VAChT expression. Pre-collected histological samples will be analyzed from genetically modified mice (VAChT-KD) that were exposed to ambient air at two distinct sites in Vitória (Brazil), during both summer and winter, each with varying pollution levels. These animals had received intratracheal elastase and were maintained under controlled conditions throughout exposure.The analysis will include immunohistochemistry for inflammatory markers (IL-1¿, IL-6, IL-17, TNF-¿), tissue remodeling proteins (MMP-9, TIMP-1), oxidative stress (iNOS), NF-¿B pathway activation, and bronchial angiogenesis. Morphometric quantification will be performed using microscopy and standardized stereological methods. Statistical analyses will include ANOVA and Rank Sum tests, with significance set at p<0.05.This study is innovative in integrating real-world exposure to iron-derived PM with cholinergic system modulation in an experimental COPD model. The results are expected to enhance understanding of the cellular and molecular mechanisms linking pollution to chronic lung disease progression, and may support the development of new therapeutic strategies and public health policies for industrialized regions.