NO2 exposure contributes to cardiac hypertrophy in male mice through apoptosis signaling pathways.

Nitrogen dioxide (NO2) is one of the most common indoor and outdoor air pollutants. Inhalation of NO2 is associated with an increased risk of health problems, especially cardiovascular diseases. However, the underlying pathogenic mechanisms still remain unclear. In this study, we exposed C57BL/6J mice to NO2 (2.5 ppm, 5 h/d) for 28 days and found that NO2 inhalation induced cardiac dysfunction in male mice, but not in female mice, including left ventricular dilation and cardiac systolic dysfunction. Pathological staining showed that NO2 inhalation induced eccentric hypertrophy with enlarged individual cardiomyocytes, dilated left ventricle, and thinning of the left ventricular wall in male mice. The transcriptional analysis suggested that NO2 exposure could disrupt Ca2+ homeostasis, actin cytoskeletal reorganization, myocardial contractility, and vascular dilation in male mice. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that differentially expressed genes (DEGs) were closely associated with the apoptotic signaling pathways. These findings suggested that NO2 exposure caused cardiac eccentric hypertrophy and cardiac dysfunction through apoptotic signaling pathways, and contributed to cardiotoxicity.