细胞色素C氧化酶5A (COX5A)对线粒体紊乱和氧化应激在VSMC表型调节和内膜形成中的保护作用

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Haijing Guan, Jingwen Sun, Xiuying Liang, Wenjuan Yao
{"title":"细胞色素C氧化酶5A (COX5A)对线粒体紊乱和氧化应激在VSMC表型调节和内膜形成中的保护作用","authors":"Haijing Guan,&nbsp;Jingwen Sun,&nbsp;Xiuying Liang,&nbsp;Wenjuan Yao","doi":"10.2174/1570161121666230315142507","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The pathological role of cytochrome c oxidase 5A (COX5A) in vascular neointima formation remains unknown.</p><p><strong>Aim: </strong>This study aims to investigate the role of COX5A on platelet-derived growth factor BB (PDGFBB)- mediated smooth muscle phenotypic modulation and neointima formation and clarify the molecular mechanisms behind this effect.</p><p><strong>Methods: </strong>For <i>in vitro assays</i>, human aortic vascular smooth muscle cells (HA-VSMCs) were transfected with pcDNA3.1-COX5A and COX5A siRNA to overexpress and knockdown COX5A, respectively. Mitochondrial complex IV activity, oxygen consumption rate (OCR), H<sub>2</sub>O<sub>2</sub> and ATP production, reactive oxygen species (ROS) generation, cell proliferation, and migration were measured. For in vivo assays, rats after balloon injury (BI) were injected with recombinant lentivirus carrying the COX5A gene. Mitochondrial COX5A expression, carotid arterial morphology, mitochondrial ultrastructure, and ROS were measured.</p><p><strong>Results: </strong>The results showed that PDGF-BB reduced the level and altered the distribution of COX5A in mitochondria, as well as reduced complex IV activity, ATP synthesis, and OCR while increasing H<sub>2</sub>O<sub>2</sub> synthesis, ROS production, and cell proliferation and migration. These effects were reversed by overexpression of COX5A and aggravated by COX5A knockdown. In addition, COX5A overexpression attenuated BI-induced neointima formation, muscle fiber area ratio, VSMC migration to the intima, mitochondrial ultrastructural damage, and vascular ROS generation.</p><p><strong>Conclusion: </strong>The present study demonstrated that COX5A protects VSMCs against phenotypic modulation by improving mitochondrial respiratory function and attenuating mitochondrial damage, as well as reducing oxidative stress, thereby preventing neointima formation.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Protective Role of Cytochrome C Oxidase 5A (COX5A) against Mitochondrial Disorder and Oxidative Stress in VSMC Phenotypic Modulation and Neointima Formation.\",\"authors\":\"Haijing Guan,&nbsp;Jingwen Sun,&nbsp;Xiuying Liang,&nbsp;Wenjuan Yao\",\"doi\":\"10.2174/1570161121666230315142507\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The pathological role of cytochrome c oxidase 5A (COX5A) in vascular neointima formation remains unknown.</p><p><strong>Aim: </strong>This study aims to investigate the role of COX5A on platelet-derived growth factor BB (PDGFBB)- mediated smooth muscle phenotypic modulation and neointima formation and clarify the molecular mechanisms behind this effect.</p><p><strong>Methods: </strong>For <i>in vitro assays</i>, human aortic vascular smooth muscle cells (HA-VSMCs) were transfected with pcDNA3.1-COX5A and COX5A siRNA to overexpress and knockdown COX5A, respectively. Mitochondrial complex IV activity, oxygen consumption rate (OCR), H<sub>2</sub>O<sub>2</sub> and ATP production, reactive oxygen species (ROS) generation, cell proliferation, and migration were measured. For in vivo assays, rats after balloon injury (BI) were injected with recombinant lentivirus carrying the COX5A gene. Mitochondrial COX5A expression, carotid arterial morphology, mitochondrial ultrastructure, and ROS were measured.</p><p><strong>Results: </strong>The results showed that PDGF-BB reduced the level and altered the distribution of COX5A in mitochondria, as well as reduced complex IV activity, ATP synthesis, and OCR while increasing H<sub>2</sub>O<sub>2</sub> synthesis, ROS production, and cell proliferation and migration. These effects were reversed by overexpression of COX5A and aggravated by COX5A knockdown. In addition, COX5A overexpression attenuated BI-induced neointima formation, muscle fiber area ratio, VSMC migration to the intima, mitochondrial ultrastructural damage, and vascular ROS generation.</p><p><strong>Conclusion: </strong>The present study demonstrated that COX5A protects VSMCs against phenotypic modulation by improving mitochondrial respiratory function and attenuating mitochondrial damage, as well as reducing oxidative stress, thereby preventing neointima formation.</p>\",\"PeriodicalId\":2,\"journal\":{\"name\":\"ACS Applied Bio Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Bio Materials\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/1570161121666230315142507\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1570161121666230315142507","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0

摘要

背景:细胞色素c氧化酶5A (COX5A)在血管新生内膜形成中的病理作用尚不清楚。目的:本研究旨在探讨COX5A在血小板衍生生长因子BB (PDGFBB)介导的平滑肌表型调节和新生内膜形成中的作用,并阐明其分子机制。方法:体外实验采用pcDNA3.1-COX5A和COX5A siRNA转染人主动脉血管平滑肌细胞(HA-VSMCs),分别过表达和低表达COX5A。测定线粒体复合体IV活性、耗氧率(OCR)、H2O2和ATP生成、活性氧(ROS)生成、细胞增殖和迁移。在体内实验中,给球囊损伤(BI)后的大鼠注射携带COX5A基因的重组慢病毒。检测线粒体COX5A表达、颈动脉形态、线粒体超微结构和ROS。结果:结果显示PDGF-BB降低线粒体中COX5A的水平并改变其分布,降低复合物IV活性、ATP合成和OCR,同时增加H2O2合成、ROS生成和细胞增殖和迁移。这些作用可被过表达的COX5A逆转,并因COX5A的下调而加重。此外,COX5A过表达可减弱bi诱导的新内膜形成、肌纤维面积比、VSMC向内膜迁移、线粒体超微结构损伤和血管ROS生成。结论:本研究表明,COX5A通过改善线粒体呼吸功能,减轻线粒体损伤,减少氧化应激,从而防止新内膜的形成,从而保护VSMCs免受表型调节。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Protective Role of Cytochrome C Oxidase 5A (COX5A) against Mitochondrial Disorder and Oxidative Stress in VSMC Phenotypic Modulation and Neointima Formation.

Background: The pathological role of cytochrome c oxidase 5A (COX5A) in vascular neointima formation remains unknown.

Aim: This study aims to investigate the role of COX5A on platelet-derived growth factor BB (PDGFBB)- mediated smooth muscle phenotypic modulation and neointima formation and clarify the molecular mechanisms behind this effect.

Methods: For in vitro assays, human aortic vascular smooth muscle cells (HA-VSMCs) were transfected with pcDNA3.1-COX5A and COX5A siRNA to overexpress and knockdown COX5A, respectively. Mitochondrial complex IV activity, oxygen consumption rate (OCR), H2O2 and ATP production, reactive oxygen species (ROS) generation, cell proliferation, and migration were measured. For in vivo assays, rats after balloon injury (BI) were injected with recombinant lentivirus carrying the COX5A gene. Mitochondrial COX5A expression, carotid arterial morphology, mitochondrial ultrastructure, and ROS were measured.

Results: The results showed that PDGF-BB reduced the level and altered the distribution of COX5A in mitochondria, as well as reduced complex IV activity, ATP synthesis, and OCR while increasing H2O2 synthesis, ROS production, and cell proliferation and migration. These effects were reversed by overexpression of COX5A and aggravated by COX5A knockdown. In addition, COX5A overexpression attenuated BI-induced neointima formation, muscle fiber area ratio, VSMC migration to the intima, mitochondrial ultrastructural damage, and vascular ROS generation.

Conclusion: The present study demonstrated that COX5A protects VSMCs against phenotypic modulation by improving mitochondrial respiratory function and attenuating mitochondrial damage, as well as reducing oxidative stress, thereby preventing neointima formation.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信