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硝酸钠通过miR-34a/FGF-21轴调节载脂蛋白E基因敲除小鼠的衰老并伴有主动脉粥样硬化。

Sodium nitrate regulates senescence accompanied by aortic atherosclerosis in ApoE mice through the miR-34a/FGF-21 axis.

作者信息

Tao Ning, He Zhichao, Duan Han, Wang Liang, Yi Jing, Shao Jingyuan, Lv Lin, Duan Junzhao, Cao Hu, Dong Xiwen, Wang Hua

机构信息

College of Life Science, Anhui Medical University, Hefei, China.

Academy of Military Medical Sciences, Beijing Institute of Radiation Medicine, Beijing, China.

出版信息

Front Pharmacol. 2025 Mar 5;16:1562321. doi: 10.3389/fphar.2025.1562321. eCollection 2025.

DOI:10.3389/fphar.2025.1562321
PMID:40110129
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11919828/
Abstract

INTRODUCTION

Increasing evidence indicates that cellular senescence is a significant risk factor for atherosclerosis (AS).

METHODS

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 HO-induced human arterial endothelial cell (HAoEC) senescence model was established to verify the role of miR-34a in AS-associated senescence.

RESULTS

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, 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.

DISCUSSION

These findings might lead to the introduction of a new therapy for senescence-related diseases in the future.

摘要

引言

越来越多的证据表明细胞衰老 是动脉粥样硬化（AS）的一个重要风险因素。

方法

在本研究中，我们使用载脂蛋白E基因敲除（ApoE）小鼠模型来研究硝酸钠对伴随动脉粥样硬化的衰老的影响。硝酸钠干预后，评估小鼠主动脉中AS病理变化程度和细胞衰老变化情况。同时，建立血红素加氧酶诱导的人动脉内皮细胞（HAoEC）衰老模型，以验证miR-34a在AS相关衰老中的作用。

结果

我们观察到硝酸钠减少了油红O阳性面积，降低了血清胆固醇（CHO）和甘油三酯（TG）浓度，并减轻了ApoE小鼠的炎症反应。此外，硝酸钠处理后，主动脉中SA-β-Gal阳性面积、细胞周期调控相关基因和miR-34a的表达均下降。此外，硝酸钠通过抑制miR-34a的表达上调FGF21的表达，从而挽救HAoECs的衰老表型。这些结果表明，硝酸钠可通过调节miR-34a/FGF21轴挽救内皮细胞衰老表型并减轻ApoE小鼠的主动脉粥样硬化。

讨论

这些发现可能会在未来带来针对衰老相关疾病的新疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a16/11919828/ef42918d110a/fphar-16-1562321-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a16/11919828/f6f68167bdfc/fphar-16-1562321-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a16/11919828/eecba18f9fff/fphar-16-1562321-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a16/11919828/6b357674bcd2/fphar-16-1562321-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a16/11919828/21979fc3ac39/fphar-16-1562321-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a16/11919828/ef42918d110a/fphar-16-1562321-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a16/11919828/f6f68167bdfc/fphar-16-1562321-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a16/11919828/eecba18f9fff/fphar-16-1562321-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a16/11919828/6b357674bcd2/fphar-16-1562321-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a16/11919828/21979fc3ac39/fphar-16-1562321-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a16/11919828/ef42918d110a/fphar-16-1562321-g005.jpg

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