N‑acetyl cysteine prevents ambient fine particulate matter‑potentiated atherosclerosis via inhibition of reactive oxygen species‑induced oxidized low density lipoprotein elevation and decreased circulating endothelial progenitor cell

Yixin Xu; Haoran Bu; Yufan Jiang; Xiaoqing Zhuo; Ke Hu; Zhihua Si; Yong Chen; Qiwei Liu; Xianwei Gong; Haihui Sun; Qingyi Zhu; Lianqun Cui; Xiaochun Ma; Yuqi Cui

doi:10.3892/mmr.2022.12752

N‑acetyl cysteine prevents ambient fine particulate matter‑potentiated atherosclerosis via inhibition of reactive oxygen species‑induced oxidized low density lipoprotein elevation and decreased circulating endothelial progenitor cell

Mol Med Rep. 2022 Jul;26(1):236. doi: 10.3892/mmr.2022.12752. Epub 2022 May 27.

Authors

Yixin Xu¹, Haoran Bu², Yufan Jiang¹, Xiaoqing Zhuo², Ke Hu³, Zhihua Si³, Yong Chen², Qiwei Liu¹, Xianwei Gong⁴, Haihui Sun¹, Qingyi Zhu⁵, Lianqun Cui¹, Xiaochun Ma⁶, Yuqi Cui¹

Affiliations

¹ Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China.
² Department of Cardiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, P.R. China.
³ Department of Emergency, Qianfoshan Hospital, Shandong First Medical University, Jinan, Shandong 250014, P.R. China.
⁴ Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China.
⁵ Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
⁶ Department of Cardiovascular Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China.

Abstract

Ambient fine particulate matter (PM) serves an important role in the development of cardiovascular disease, including atherosclerosis. Antioxidant N‑acetyl cysteine (NAC) has protective effects in the cardiovascular system. However, it is unknown if NAC prevents PM‑potentiated atherosclerosis in hyperlipidemia. Low‑density lipoprotein (LDL) receptor knockout mice were pretreated with 1 mg/ml NAC in drinking water for 1 week and continued to receive NAC, high‑fat diet and intranasal instillation of PM for 1 week or 6 months. Blood plasma was collected for lipid profile, oxidized (ox‑)LDL, blood reactive oxygen species (ROS) and inflammatory cytokine (TNF‑α, IL‑1β and IL‑6) measurement. Blood cells were harvested for endothelial progenitor cell (EPC) population and intracellular ROS analysis. Murine aorta was isolated for atherosclerotic plaque ratio calculation. NAC treatment maintained circulating EPC level and significantly decreased blood ox‑LDL and ROS, inflammatory cytokines, mononuclear and EPC intracellular ROS levels as well as aortic plaque ratio. NAC prevented PM‑potentiated atherosclerosis by inhibiting plasma ROS‑induced ox‑LDL elevation, mononuclear cell and EPC intracellular ROS‑induced circulating EPC reduction and inflammatory cytokine production.

Keywords: N‑acetyl cysteine; air pollution; endothelial progenitor cells; hyperlipidemia; inflammation; oxidized low density lipoprotein; particulate matter; reactive oxygen species.

MeSH terms

Acetylcysteine / pharmacology
Animals
Atherosclerosis* / drug therapy
Endothelial Progenitor Cells*
Lipoproteins, LDL / pharmacology
Mice
Particulate Matter / toxicity
Reactive Oxygen Species

Substances

Lipoproteins, LDL
Particulate Matter
Reactive Oxygen Species
oxidized low density lipoprotein
Acetylcysteine

Grants and funding

The present study was supported by The National Nature Science Foundation of China (grant nos. 81600222 and 81800255), Young Experts of Taishan Scholar Program of Shandong Province (grant no. tsqn201812142), Academic Promotion Programme of Shandong First Medical University (grant nos. 2019RC017), The Natural Science Foundation of Shandong Province (grant nos. ZR2016HM22, ZR2018BH002, ZR2020MH044 and ZR2021MH112) and Clinical Medical Science and Technology Innovation Development Plan Project of Jinan in China (grant no. 201704106).