AMPKα2 deficiency exacerbates long-term PM2.5 exposure-induced lung injury and cardiac dysfunction

• Published in: Free radical biology & medicine 2018-06, Vol.121, p.202-214
• Main Authors: Wang, Hongyun, Shen, Xiyue, Tian, Guoxiong, Shi, Xili, Huang, Wei, Wu, Yongguang, Sun, Lei, Peng, Can, Liu, Shasha, Huang, Ying, Chen, Xiaoyu, Zhang, Fang, Chen, Yingjie, Ding, Wenjun, Lu, Zhongbing
• Format: Article
• Language: English
• Subjects: AMPK; Heart failure; Lung injury; PM2.5; Prdx5
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2018.05.008

Previous studies have demonstrated that long-term exposure to fine particulate matter (PM2.5) 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 PM2.5 has not been investigated. In this study, we exposed wild-type (WT) and AMPKα2-/- mice to either airborne PM2.5 (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 PM2.5-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 PM2.5-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 PM2.5 exposure. Our findings suggest that strategies to increase AMPK activity may provide a novel approach to attenuate air pollution associated disease. [Display omitted] •AMPKα2 deficiency exacerbates long-term PM2.5 exposure-induced lung injury and heart failure.•AMPKα2 deficiency exacerbates PM2.5-induced oxidative stress through downregulation of Prdx5.•NF-κB was activated in lungs of PM2.5-exposed AMPKα2-/- mice.•Inhibition of AMPK activity exacerbated PM2.5-induced cell death and oxidative stress.