Carotid Plaque‐Derived Small Extracellular Vesicles Mediate Atherosclerosis and Correlate With Plaque Vulnerability
ABSTRACT Carotid plaque‐derived small extracellular vesicles (psEVs) offer insights into tissue‐ and disease‐specific pathobiology, but their roles in plaque vulnerability and their diagnostic potential remain unclear. Herein, we isolated psEVs from stable and vulnerable (intraplaque hemorrhage [IPH...
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Wiley
2025-06-01
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| Online Access: | https://doi.org/10.1002/mco2.70220 |
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| author | Xin Xu Taoyuan Lu Yao Feng Wenbo Cao Dianwei Liu Peng Gao Yan Ma Yabing Wang Bin Yang Yanfei Chen Jian Chen Ran Xu Xinyu Wang Lebin Chen Yuanyuan Ji Liqun Jiao |
| author_facet | Xin Xu Taoyuan Lu Yao Feng Wenbo Cao Dianwei Liu Peng Gao Yan Ma Yabing Wang Bin Yang Yanfei Chen Jian Chen Ran Xu Xinyu Wang Lebin Chen Yuanyuan Ji Liqun Jiao |
| author_sort | Xin Xu |
| collection | DOAJ |
| description | ABSTRACT Carotid plaque‐derived small extracellular vesicles (psEVs) offer insights into tissue‐ and disease‐specific pathobiology, but their roles in plaque vulnerability and their diagnostic potential remain unclear. Herein, we isolated psEVs from stable and vulnerable (intraplaque hemorrhage [IPH] or fibrous cap rupture [FCR]) plaques in patients with asymptomatic carotid artery stenosis (aCAS). Our findings demonstrated that psEVs alone were sufficient to induce inflammatory endothelial dysfunction in vitro and exacerbate atherogenesis in ApoE‐deficient mice. MicroRNA sequencing of psEVs (sequencing cohort, n = 18) identified 21 differentially expressed microRNAs (DEmiRNAs) distinguishing stable and vulnerable plaques, and 41 DEmiRNAs differentiating IPH from FCR subtypes. Subsequent validation using qRT‐PCR and the High‐throughput nano‐bio chip integrated system for liquid biopsy system revealed that plasma‐derived sEV miR‐497‐5p, miR‐152‐3p, and miR‐204‐5p effectively differentiated stable plaques from vulnerable plaques, while miR‐23a‐3p and miR‐143‐5p further distinguished IPH from FCR subtypes, in both the discovery cohort (n = 178) and an independent external cohort (n = 82). Mechanistic investigations identified miR‐497‐5p as a key mediator of vulnerable psEVs' proinflammatory and proatherogenic effects through directly targeting atheroprotective uncoupling protein 2 (UCP2). These findings highlight the roles of psEVs in atherogenesis and plaque vulnerability, providing valuable insights for risk stratification and therapeutic decision‐making in aCAS patients. |
| format | Article |
| id | doaj-art-3dd13f9952ec4e5c97fff565fb22b6c4 |
| institution | DOAJ |
| issn | 2688-2663 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-3dd13f9952ec4e5c97fff565fb22b6c42025-08-20T02:56:34ZengWileyMedComm2688-26632025-06-0166n/an/a10.1002/mco2.70220Carotid Plaque‐Derived Small Extracellular Vesicles Mediate Atherosclerosis and Correlate With Plaque VulnerabilityXin Xu0Taoyuan Lu1Yao Feng2Wenbo Cao3Dianwei Liu4Peng Gao5Yan Ma6Yabing Wang7Bin Yang8Yanfei Chen9Jian Chen10Ran Xu11Xinyu Wang12Lebin Chen13Yuanyuan Ji14Liqun Jiao15Department of Neurosurgery Xuanwu Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Xuanwu Hospital, Capital Medical University Beijing ChinaDepartment of Neurology Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Neurosurgery Xuanwu Hospital, Capital Medical University Beijing ChinaXuanwu Jinan Hospital Jinan ChinaDepartment of Neurosurgery Xuanwu Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Xuanwu Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Xuanwu Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Xuanwu Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Xuanwu Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Xuanwu Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Xuanwu Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Xuanwu Hospital, Capital Medical University Beijing ChinaHangzhou Dixiang Co. Ltd. Hangzhou ChinaHangzhou Dixiang Co. Ltd. Hangzhou ChinaDepartment of Neurosurgery Xuanwu Hospital, Capital Medical University Beijing ChinaABSTRACT Carotid plaque‐derived small extracellular vesicles (psEVs) offer insights into tissue‐ and disease‐specific pathobiology, but their roles in plaque vulnerability and their diagnostic potential remain unclear. Herein, we isolated psEVs from stable and vulnerable (intraplaque hemorrhage [IPH] or fibrous cap rupture [FCR]) plaques in patients with asymptomatic carotid artery stenosis (aCAS). Our findings demonstrated that psEVs alone were sufficient to induce inflammatory endothelial dysfunction in vitro and exacerbate atherogenesis in ApoE‐deficient mice. MicroRNA sequencing of psEVs (sequencing cohort, n = 18) identified 21 differentially expressed microRNAs (DEmiRNAs) distinguishing stable and vulnerable plaques, and 41 DEmiRNAs differentiating IPH from FCR subtypes. Subsequent validation using qRT‐PCR and the High‐throughput nano‐bio chip integrated system for liquid biopsy system revealed that plasma‐derived sEV miR‐497‐5p, miR‐152‐3p, and miR‐204‐5p effectively differentiated stable plaques from vulnerable plaques, while miR‐23a‐3p and miR‐143‐5p further distinguished IPH from FCR subtypes, in both the discovery cohort (n = 178) and an independent external cohort (n = 82). Mechanistic investigations identified miR‐497‐5p as a key mediator of vulnerable psEVs' proinflammatory and proatherogenic effects through directly targeting atheroprotective uncoupling protein 2 (UCP2). These findings highlight the roles of psEVs in atherogenesis and plaque vulnerability, providing valuable insights for risk stratification and therapeutic decision‐making in aCAS patients.https://doi.org/10.1002/mco2.70220asymptomatic carotid artery stenosisatherosclerosisbiomarkerextracellular vesiclemicroRNAplaque vulnerability |
| spellingShingle | Xin Xu Taoyuan Lu Yao Feng Wenbo Cao Dianwei Liu Peng Gao Yan Ma Yabing Wang Bin Yang Yanfei Chen Jian Chen Ran Xu Xinyu Wang Lebin Chen Yuanyuan Ji Liqun Jiao Carotid Plaque‐Derived Small Extracellular Vesicles Mediate Atherosclerosis and Correlate With Plaque Vulnerability MedComm asymptomatic carotid artery stenosis atherosclerosis biomarker extracellular vesicle microRNA plaque vulnerability |
| title | Carotid Plaque‐Derived Small Extracellular Vesicles Mediate Atherosclerosis and Correlate With Plaque Vulnerability |
| title_full | Carotid Plaque‐Derived Small Extracellular Vesicles Mediate Atherosclerosis and Correlate With Plaque Vulnerability |
| title_fullStr | Carotid Plaque‐Derived Small Extracellular Vesicles Mediate Atherosclerosis and Correlate With Plaque Vulnerability |
| title_full_unstemmed | Carotid Plaque‐Derived Small Extracellular Vesicles Mediate Atherosclerosis and Correlate With Plaque Vulnerability |
| title_short | Carotid Plaque‐Derived Small Extracellular Vesicles Mediate Atherosclerosis and Correlate With Plaque Vulnerability |
| title_sort | carotid plaque derived small extracellular vesicles mediate atherosclerosis and correlate with plaque vulnerability |
| topic | asymptomatic carotid artery stenosis atherosclerosis biomarker extracellular vesicle microRNA plaque vulnerability |
| url | https://doi.org/10.1002/mco2.70220 |
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