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Astragalus Polysaccharides Reduce High-glucose-induced Rat Aortic Endothelial Cell Senescence and Inflammasome Activation by Modulating the Mitochondrial Na+/Ca2+ Exchanger

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Abstract

Vascular endothelial cells play a vital role in atherosclerotic changes and the progression of cardiovascular disease in older adults. Previous studies have indicated that Astragalus polysaccharides (APS), a main active component of the traditional Chinese medicine Astragalus, protect mitochondria and exert an antiaging effect in the mouse liver and brain. However, the effect of APS on rat aortic endothelial cell (RAEC) senescence and its underlying mechanism have not been investigated. In this study, we extracted RAECs from 2-month-old male Wistar rats by the tissue explant method and found that APS ameliorated the high-glucose-induced increase in the frequency of SA-β-Gal positivity and the levels of the senescence-related proteins p16, p21, and p53. APS increased the tube formation capacity of RAECs under high-glucose conditions. Moreover, APS enhanced the expression of the mitochondrial Na+/Ca2+ exchanger NCLX, and knockdown of NCLX by small interfering RNA (siRNA) transfection suppressed the antiaging effect of APS under high-glucose conditions. Additionally, APS ameliorated RAEC mitochondrial dysfunction, including increasing ATP production, cytochrome C oxidase activity and the oxygen consumption rate (OCR), and inhibited high-glucose-induced NLRP3 inflammasome activation and IL-1β release, which were reversed by siNCLX. These results indicate that APS reduces high-glucose-induced inflammasome activation and ameliorates mitochondrial dysfunction and senescence in RAECs by modulating NCLX. Additionally, APS enhanced the levels of autophagy-related proteins (LC3B-II/I, Atg7) and increased the quantity of autophagic vacuoles under high-glucose conditions. Therefore, these data demonstrate that APS may reduce vascular endothelial cell inflammation and senescence through NCLX.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

APS:

Astragalus polysaccharides

RAECs:

Rat aortic endothelial cells

SA-β-gal:

Senescence-associated β-galactosidase

IL-1β:

Interleukin-1β

CVD:

Cardiovascular diseases

ROS:

Reactive oxygen species

NLRP3:

NOD-like receptor family pyrin domain-containing 3

ECL:

Enhanced chemiluminescence

IgG:

Immunoglobulin G

Con:

Control

HG:

High glucose

ATP:

Adenosine triphosphate

COX:

Cytochrome c oxidase

OCR:

Oxygen consumption rate

FCCP:

carbonyl cyanide-p-trifluoromethoxyphenylhydrazone

Atg:

Autophagy

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Acknowledgements

The authors would like to express their sincere gratitude to all the researchers at the Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases. This study was supported by grants from the National Natural Science Foundation of China (No. 81774119, 81300265, 81900765); Special Scientific Research Project of Military Healthcare (19BJZ29), and Beijing Haidian District Health Development Research and Cultivation Program (No. HP2021-03-80303).

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  1. These authors contributed equally: Xin-Yu Miao, Xiao-Xiao Zhu

Authors and Affiliations

  1. Department of Endocrinology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China

    Xin-Yu Miao, Xiao-Xiao Zhu, Zhao-Yan Gu, Ling-Jun Rong, Fan Hu, Yan-Ping Gong & Chun-Lin Li

  2. Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China

    Bo Fu, Shao-Yuan Cui & Xiang-Mei Chen

  3. Department of Blood Purification, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

    Yuan Zu

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  1. Xin-Yu Miao
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Miao, XY., Zhu, XX., Gu, ZY. et al. Astragalus Polysaccharides Reduce High-glucose-induced Rat Aortic Endothelial Cell Senescence and Inflammasome Activation by Modulating the Mitochondrial Na+/Ca2+ Exchanger. Cell Biochem Biophys 80, 341–353 (2022). https://doi.org/10.1007/s12013-021-01058-w

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