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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Translational Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1562321
This article is part of the Research Topic Nutrition as a Pharmacological Approach to Metabolic Disorders and Ageing View all 5 articles
Sodium nitrate regulates senescence accompanied by aortic atherosclerosis in ApoE -/-mice through the miR-34a/FGF-21 axis
Provisionally accepted
Ning Tao 1 Zhichao He 1 Han Duan 2 Liang Wang 1 Jing Yi 2 Jingyuan Shao 2 Lin Lv 2 Junzhao Duan 2 Hu Cao 2
Xiwen Dong 3
Hua Wang 2*- 1 School of Life Sciences, Anhui Medical University, Hefei, Anhui Province, China
- 2 Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences (AMMS), Beijing, China
- 3 Air Force General Hospital PLA, Beijing, Beijing Municipality, China
Increasing evidence indicates that cellular senescence is a significant risk factor for atherosclerosis (AS). In the present study, we used an apolipoprotein E knockout (ApoE−/−) mouse model to address the effect of sodium nitrate on senescence accompanied by atherosclerosis. After sodium nitrate intervention, the degree of AS pathological and cellular senescence changes was evaluated in mouse aortic. At the same time, an H2O2-induced human arterial endothelial cell (HAoEC) senescence model was established to verify the role of miR-34a in AS-associated senescence. We observed that sodium nitrate decreased the Oil Red O-positive area, reduced the serum cholesterol (CHO) and triglyceride (TG) concentrations, and relieved inflammatory reactions in ApoE−/− mice. Moreover, in the SA-β-Gal-positive area, the expression of cell cycle regulation-related genes and miR-34a in the aorta decreased after sodium nitrate treatment. Furthermore, sodium nitrate upregulated the expression of FGF21 by inhibiting the expression of miR-34a, thereby rescuing the senescent phenotype of HAoECs. These results suggested that sodium nitrate could rescue the endothelial cell senescence phenotype and alleviate aortic atherosclerosis in ApoE−/− mice by regulating the miR-34a/FGF21 axis. These findings might lead to the introduction of a new therapy for senescence-related diseases in the future.
Keywords: Atherosclerosis, senescence, Sodium nitrate, miR-34a, FGF21
Received: 17 Jan 2025; Accepted: 17 Feb 2025.
Copyright: © 2025 Tao, He, Duan, Wang, Yi, Shao, Lv, Duan, Cao, Dong and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Hua Wang, Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences (AMMS), Beijing, China
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