Abstract Body: Research Question / Hypothesis
We hypothesised that exposure to particulate air pollution activates biological pathways, including endothelial dysfunction, dysautonomia, and excessive inflammation, promoting pulmonary vascular remodelling and right ventricular dysfunction.
Goals
To synthesise experimental, translational, and epidemiological evidence explaining how air pollution influences pulmonary vascular physiology and right ventricular function.
Methods
A narrative synthesis of the existing literature, including cellular experiments, human observational studies, and animal models, was conducted to examine the cardiopulmonary effects of air pollution. Key mechanistic pathways linking particulate matter exposure to pulmonary vascular and right ventricular dysfunction were identified.
Results
Evidence from observational and clinical studies provides evidence that particulate matter exposure causes pathological changes in the pulmonary vasculature and the right ventricle. Inhaled particles promote oxidative stress and inflammatory signalling in pulmonary endothelial and smooth muscle cells. This causes endothelial dysfunction and pulmonary vascular remodelling, resulting in increased pulmonary vascular resistance. Studies show that for each 5 µg/m3 increase in fine particulate matter (PM2.5), the risk of developing PH increases by 8%. Experimental studies have shown that heavy metals, such as zinc embedded in particulate matter, can cause mitochondrial dysfunction and trigger inflammatory pathways that damage the pulmonary vasculature and lead to fibrosis. Additionally, exposure to pollution has been shown to disrupt autonomic balance, leading to enhanced sympathetic activation, which can contribute to arrhythmias and ventricular dysfunction. Epidemiologic studies also show an association of particulate matter exposure and increased risk of PH, right ventricular hypertrophy and heart failure, particularly among individuals with underlying COPD and cardiovascular disease.
Conclusions
Air pollution is an important environmental determinant of pulmonary vascular dysfunction. Exposure to particulate matter can lead to the development of PH and right ventricular dysfunction. Pathophysiologic mechanisms include oxidative stress, unregulated inflammation, endothelial injury, and dysautonomia. These findings highlight pollution as a modifiable risk factor for PH and underscore the need for further mechanistic and translational research to clarify causal mechanisms.