AMPKα2 deficiency exacerbates long-term PM_2.5 exposure-induced lung injury and cardiac dysfunction

Previous studies have demonstrated that long-term exposure to fine particulate matter (PM_2.5) increases the risk of respiratory and cardiovascular diseases. As a metabolic sensor, AMP-activated protein kinase (AMPK) is a promising target for cardiovascular disease. However, the impact of AMPK on the adverse health effects of PM_2.5 has not been investigated. In this study, we exposed wild-type (WT) and AMPKα2^-/- mice to either airborne PM_2.5 (mean daily concentration ~64 µg/m³) or filtered air for 6 months through a whole-body exposure system. After exposure, AMPKα2^-/- mice developed severe lung injury and left ventricular dysfunction. In the PM_2.5-exposed lungs and hearts, loss of AMPKα2 resulted in higher levels of fibrotic genes, more collagen deposition, lower levels of peroxiredoxin 5 (Prdx5), and greater induction of oxidative stress and inflammation than observed in the lungs and hearts of WT mice. In PM_2.5-exposed BEAS-2B and H9C2 cells, inhibition of AMPK activity significantly decreased cell viability and Prdx5 expression, and increased the intracellular ROS and p-NF-κB levels. Collectively, our results provide the first direct evidence that AMPK has a marked protective effect on the adverse health effects induced by long-term PM_2.5 exposure. Our findings suggest that strategies to increase AMPK activity may provide a novel approach to attenuate air pollution associated disease.