PM2.5-induced premature senescence in HUVECs through the SIRT1/PGC-1α/SIRT3 pathway

Qing Yan; Rao Zheng; Yi Li; Juan Hu; Meidi Gong; Manman Lin; Xuecong Xu; Jing Wu; Shikun Sun

doi:10.1016/j.scitotenv.2024.171177

PM_2.5-induced premature senescence in HUVECs through the SIRT1/PGC-1α/SIRT3 pathway

Sci Total Environ. 2024 Apr 15:921:171177. doi: 10.1016/j.scitotenv.2024.171177. Epub 2024 Feb 23.

Authors

Qing Yan¹, Rao Zheng¹, Yi Li¹, Juan Hu¹, Meidi Gong¹, Manman Lin¹, Xuecong Xu¹, Jing Wu², Shikun Sun³

Affiliations

¹ Department of Toxicology, School of Public Health, Medical College of Soochow University, Suzhou 215123, Jiangsu, China.
² Department of Toxicology, School of Public Health, Medical College of Soochow University, Suzhou 215123, Jiangsu, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China. Electronic address: wujing88@suda.edu.cn.
³ Department of Cardiology, First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address: sunshikun@suda.edu.cn.

PMID: 38402989
DOI: 10.1016/j.scitotenv.2024.171177

Abstract

Vascular endothelial cell senescence plays a pivotal role in the development of atherosclerosis. Recent studies have demonstrated that ambient fine particulate matter (PM_2.5) induces stress-induced premature senescence (SIPS) in vascular endothelial cells. However, the precise mechanisms underlying this process remain to be fully elucidated. Cellular senescence is closely associated with reactive oxygen species (ROS), and emerging research has established a strong connection between the SIRT1/PGC-1α/SIRT3 signaling pathway and the antioxidant system in vascular endothelial cells. In this study, we aimed to investigate the impact of PM_2.5 on vascular endothelial cell senescence and to elucidate the underlying mechanisms. Our findings revealed that PM_2.5 exposure led to an increase in senescence-associated β-galactosidase (SA-β-gal) activity and the expression of the cell cycle-blocking proteins P53/P21 and P16 in human umbilical vein endothelial cells (HUVECs). Flow cytometry analysis demonstrated an elevated proportion of cells arrested in the G0/G1 phase after PM_2.5 exposure. In addition, PM_2.5-induced cellular senescence was attributed to the disruption of the cellular antioxidative defense system through the SIRT1/PGC-1α/SIRT3 signaling pathway. The expression of cellular senescence markers was reduced after targeted scavenging of mitochondrial ROS using MitoQ. Moreover, treatment with SRT1720, a SIRT1-specific activator, upregulated the SIRT1/PGC-1α/SIRT3 signaling pathway, restored the antioxidant system, and attenuated the expression of cellular senescence markers. Taken together, our results suggest that PM_2.5 downregulates the SIRT1/PGC-1α/SIRT3 signaling pathway, resulting in impaired antioxidant defenses in HUVECs. This, in turn, allows for the accumulation of ROS, leading to inhibition of endothelial cell cycle progression and the onset of stress-induced senescence in HUVECs.

Keywords: Antioxidant defense; HUVECs; PM(2.5); SIRT1/PGC-1α/SIRT3 pathway; Stress-induced premature senescence.

MeSH terms

Antioxidants / metabolism
Human Umbilical Vein Endothelial Cells
Humans
Oxidative Stress
Reactive Oxygen Species / metabolism
Sirtuin 1 / metabolism
Sirtuin 3* / metabolism

Substances

Sirtuin 3
Reactive Oxygen Species
Antioxidants
Sirtuin 1
SIRT1 protein, human
SIRT3 protein, human