PM2.5 is a well-known air pollutant threatening public health, and long-term exposure to PM2.5 increases the risk of cardiovascular diseases. Nrf2 plays a pivotal role in the amelioration of PM2.5-induced lung injury. However, if Nrf2 is involved in PM2.5-induced heart injury, and the underlying molecular mechanisms have not been explored. In this study, wild type (Nrf2+/+) and Nrf2 knockout (Nrf2-/-) mice were exposed to PM2.5 for 6 months. After PM2.5 exposure, Nrf2-/- mice developed severe physiological changes, lung injury and cardiac dysfunction. In the PM2.5-exposed hearts, Nrf2 deficiency caused significant collagen accumulation through promoting the expression of fibrosis-associated signals. Additionally, Nrf2-/- mice exhibited greater oxidative stress in cardiac tissues after PM2.5 exposure. Furthermore, PM2.5-induced inflammation in heart samples were accelerated in Nrf2-/- mice through promoting inhibitor of α/nuclear factor κB (IκBα/NF-κB) signaling pathways. We also found that Nrf2-/- aggravated autophagy initiation and glucose metabolism disorder in hearts of mice with PM2.5 challenge. Cardiac receptor-interacting protein kinase 3 (RIPK3) expression triggered by PM2.5 was further enhanced in mice with the loss of Nrf2. Collectively, these results suggested that strategies for enhancing Nrf2 could be used to treat PM2.5-induced cardiovascular diseases.
Keywords: Nrf2; PM 2.5; RIPK3; cardiomyopathy; mitochondrial dysfunction.