Melatonin alleviates PM2.5-triggered macrophage M1 polarization and atherosclerosis via regulating NOX2-mediated oxidative stress homeostasis.

Abstract

It is reported that oxidative stress homeostasis was involved in PM2.5-induced foam cell formation and progression of atherosclerosis, but the exact molecular mechanism is still unclear. Melatonin is an effective antioxidant that could reverse the cardiopulmonary injury. The main purpose of this study is to investigate the latent mechanism of PM2.5-triggered atherosclerosis development and the protective role of melatonin administration. Vascular Doppler ultrasound showed that PM2.5 exposure reduced aortic elasticity in ApoE-/- mice. Meanwhile, blood biochemical and pathological analysis demonstrated that PM2.5 exposure caused dyslipidemia, elicited oxidative damage of aorta and was accompanied by an increase in atherosclerotic plaque area; while the melatonin administration could effectively alleviate PM2.5-induced macrophage M1 polarization and atherosclerosis in mice. Further investigation verified that NADPH oxidase 2 (NOX2) and mitochondria are two prominent sources of PM2.5-induced ROS production in vascular macrophages. Whereas, the combined use of two ROS-specific inhibitors and adopted with melatonin markedly rescued PM2.5-triggered macrophage M1 polarization and foam cell formation by inhibiting NOX2-mediated crosstalk of Keap1/Nrf2/NF-κB and TLR4/TRAF6/NF-κB signaling pathways. Our results demonstrated that NOX2-mediated oxidative stress homeostasis is critical for PM2.5-induced atherosclerosis and melatonin might be a potential treatment for air pollution-related cardiovascular diseases.

• Authors: Jiangyan Liu, Qinglin Sun, Mengqi Sun, Lisen Lin, Xiaoke Ren, Tianyu Li, Qing Xu, Zhiwei Sun, Junchao Duan
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 181 Pg. 166-179 (03 2022) ISSN: 1873-4596 [Electronic] United States
• PMID: 35149217 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Kelch-Like ECH-Associated Protein 1
• NF-E2-Related Factor 2
• Particulate Matter
• NADPH Oxidase 2
• Melatonin

Topics

• Animals
• Atherosclerosis (metabolism)
• Homeostasis
• Kelch-Like ECH-Associated Protein 1 (metabolism)
• Macrophages (metabolism)
• Melatonin (metabolism, pharmacology)
• Mice
• NADPH Oxidase 2 (genetics, metabolism)
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress
• Particulate Matter (metabolism, toxicity)