Nanosecond pulsed electric field applications rejuvenate aging endothelial cells by rescuing mitochondrial-to-nuclear retrograde communication

IF 4 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy Pub Date : 2025-12-01 Epub Date: 2025-06-18 DOI:10.1016/j.reth.2025.06.004

Meifang Yin , Jie Xiao , Guangtao Huang , Huanyu Xie , Hongwei Liu , Jianqiang Yuan , Xiaofang Liu , Anna Chiarini , Ubaldo Armato , Ilaria Dal Prà , Shumaila Ijaz , Naziat Begum , Lingyun Wang , Jun Wu

{"title":"Nanosecond pulsed electric field applications rejuvenate aging endothelial cells by rescuing mitochondrial-to-nuclear retrograde communication","authors":"Meifang Yin , Jie Xiao , Guangtao Huang , Huanyu Xie , Hongwei Liu , Jianqiang Yuan , Xiaofang Liu , Anna Chiarini , Ubaldo Armato , Ilaria Dal Prà , Shumaila Ijaz , Naziat Begum , Lingyun Wang , Jun Wu","doi":"10.1016/j.reth.2025.06.004","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Endothelial cell aging is strongly associated with mitochondrial dysfunction, particularly the disruption of mitochondrial-nuclear retrograde communication (MNRC), which is essential for sustaining cellular homeostasis and regulating crucial cellular processes. Nanosecond pulsed electric fields (nsPEF) were shown to exert biological effects by targeting mitochondria. However, the nsPEF regulation of MNRC is still unclear.</div></div><div><h3>Methods</h3><div>In this study, we set up an <em>in vitro</em> model of <span>d</span>-galactose-induced senescence in human umbilical vein endothelial cells (HUVECs) to investigate the effects of nsPEF treatment on oxidative stress, cell proliferation, mitochondrial membrane potential, and markers of MNRC (MNRC), including HIF-1α and SIRT1. Moreover, we conducted <em>in vivo</em> animal experiments to evaluate nsPEF treatment's effects on HIF-1α and SIRT1 protein expression in endothelial cells (ECs) of <em>in vivo</em> rodents' aging/senescing skin tissue, as well as to examine any later changes in vascular density within the skin.</div></div><div><h3>Results</h3><div>In vitro results showed that nsPEF treatment suppressed <span>d</span>-galactose-induced senescing effects as they rescued mitochondrial membrane potential, and activated HIF-1α and SIRT1. These effects were confirmed by concurrent reductions in SA-β-Gal activity and in ROS production, and increases in EdU-positive (DNA-synthesizing) cells. Our data showed that nsPEF treatments rescued endothelial cells from <span>d</span>-galactose senescence. Interestingly, nsPEF selectively targeted senescing cells at the tested dose, with no detectable effect on otherwise untreated (normal) HUVECs. In vivo nsPEF treatments upregulated the expression of HIF-1α and SIRT1 in ECs and promoted neoangiogenesis in aged/senescent rodents' skin.</div></div><div><h3>Conclusions</h3><div>These findings suggest that nsPEF treatments rescue ECs from aging by restoring MNRC, highlighting its potential as a therapeutic strategy for age-related vascular diseases.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 207-216"},"PeriodicalIF":4.0000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Regenerative Therapy","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2352320425001373","RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/18 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction

Endothelial cell aging is strongly associated with mitochondrial dysfunction, particularly the disruption of mitochondrial-nuclear retrograde communication (MNRC), which is essential for sustaining cellular homeostasis and regulating crucial cellular processes. Nanosecond pulsed electric fields (nsPEF) were shown to exert biological effects by targeting mitochondria. However, the nsPEF regulation of MNRC is still unclear.

Methods

In this study, we set up an in vitro model of d-galactose-induced senescence in human umbilical vein endothelial cells (HUVECs) to investigate the effects of nsPEF treatment on oxidative stress, cell proliferation, mitochondrial membrane potential, and markers of MNRC (MNRC), including HIF-1α and SIRT1. Moreover, we conducted in vivo animal experiments to evaluate nsPEF treatment's effects on HIF-1α and SIRT1 protein expression in endothelial cells (ECs) of in vivo rodents' aging/senescing skin tissue, as well as to examine any later changes in vascular density within the skin.

Results

In vitro results showed that nsPEF treatment suppressed d-galactose-induced senescing effects as they rescued mitochondrial membrane potential, and activated HIF-1α and SIRT1. These effects were confirmed by concurrent reductions in SA-β-Gal activity and in ROS production, and increases in EdU-positive (DNA-synthesizing) cells. Our data showed that nsPEF treatments rescued endothelial cells from d-galactose senescence. Interestingly, nsPEF selectively targeted senescing cells at the tested dose, with no detectable effect on otherwise untreated (normal) HUVECs. In vivo nsPEF treatments upregulated the expression of HIF-1α and SIRT1 in ECs and promoted neoangiogenesis in aged/senescent rodents' skin.

Conclusions

These findings suggest that nsPEF treatments rescue ECs from aging by restoring MNRC, highlighting its potential as a therapeutic strategy for age-related vascular diseases.

查看原文本刊更多论文

纳秒脉冲电场应用通过挽救线粒体到核的逆行通讯使老化的内皮细胞恢复活力

内皮细胞衰老与线粒体功能障碍密切相关，尤其是线粒体-核逆行通讯（MNRC）的中断，而线粒体-核逆行通讯对于维持细胞稳态和调节关键细胞过程至关重要。纳秒脉冲电场（nsPEF）通过靶向线粒体发挥生物学效应。然而，MNRC对nsPEF的监管仍不明确。方法建立d-半乳糖诱导的人脐静脉内皮细胞（HUVECs）体外衰老模型，研究nsPEF处理对氧化应激、细胞增殖、线粒体膜电位及MNRC （MNRC）标志物HIF-1α和SIRT1的影响。此外，我们进行了体内动物实验，以评估nsPEF处理对体内啮齿动物老化/衰老皮肤组织内皮细胞（ECs）中HIF-1α和SIRT1蛋白表达的影响，并检查皮肤内血管密度的任何后续变化。结果体外实验结果显示，nsPEF通过挽救线粒体膜电位，激活HIF-1α和SIRT1，抑制了d-半乳糖诱导的衰老效应。SA-β-Gal活性和ROS生成同时降低，edu阳性（dna合成）细胞增加，证实了这些影响。我们的数据显示，nsPEF治疗可使内皮细胞免于d-半乳糖衰老。有趣的是，在测试剂量下，nsPEF选择性地靶向衰老细胞，对未处理（正常）的HUVECs没有可检测到的影响。体内nsPEF处理上调ECs中HIF-1α和SIRT1的表达，促进老年/衰老啮齿动物皮肤新生血管生成。这些发现表明，nsPEF治疗通过恢复MNRC来拯救内皮细胞免于衰老，突出了其作为年龄相关血管疾病治疗策略的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Regenerative Therapy Engineering-Biomedical Engineering

CiteScore

6.00

自引率

2.30%

发文量

106

审稿时长

49 days

期刊介绍： Regenerative Therapy is the official peer-reviewed online journal of the Japanese Society for Regenerative Medicine. Regenerative Therapy is a multidisciplinary journal that publishes original articles and reviews of basic research, clinical translation, industrial development, and regulatory issues focusing on stem cell biology, tissue engineering, and regenerative medicine.