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/m 3 ) 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.
|Original language||English (US)|
|Number of pages||13|
|Journal||Free Radical Biology and Medicine|
|State||Published - Jun 2018|
- Heart failure
- Lung injury