NLRP3, conveyed via extracellular vesicles from metabolic syndrome patients, is involved in atherosclerosis development
Abstract Background Inappropriate activation of the Nod-like receptor protein 3 (NLRP3)-inflammasome contributes to atherosclerosis progression and plaque instability in patients with cardiovascular events. However, its role in the atherosclerosis is not fully understood. We sought to uncover action...
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BMC
2025-06-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02296-8 |
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| author | Xavier Vidal-Gómez Luisa Vergori Séverine Dubois Frédéric Gagnadoux Samir Henni Reuben Veerapen Olivier Meilhac Mercedes Muñoz-Picos Concepción Peiró M. Carmen Martinez Ramaroson Andriantsitohaina on behalf of Metabol Study Group |
| author_facet | Xavier Vidal-Gómez Luisa Vergori Séverine Dubois Frédéric Gagnadoux Samir Henni Reuben Veerapen Olivier Meilhac Mercedes Muñoz-Picos Concepción Peiró M. Carmen Martinez Ramaroson Andriantsitohaina on behalf of Metabol Study Group |
| author_sort | Xavier Vidal-Gómez |
| collection | DOAJ |
| description | Abstract Background Inappropriate activation of the Nod-like receptor protein 3 (NLRP3)-inflammasome contributes to atherosclerosis progression and plaque instability in patients with cardiovascular events. However, its role in the atherosclerosis is not fully understood. We sought to uncover actionable targets that could help to refine the diagnostic values of metabolic syndrome (MetS) patients by taking advantage of extracellular vesicles (EVs) to support the inflammatory hypothesis of atherosclerosis. Methods Circulating large (lEVs) and small (sEVs) EVs from non-MetS subjects and MetS patients were isolated and characterized. The involvement of NLRP3 in the effects of EVs on human aortic endothelial and smooth muscle cells (SMC) and macrophages were analyzed. The pathological relevance in human atherosclerotic lesions was investigated. Results Circulating levels of lEVs carrying NLRP3 correlated with metabolic risk factors associated with obesity and insulin resistance. Both types of EVs from MetS patients increased endothelial permeability, monocyte transmigration, SMC migration and secretion of pro-inflammatory molecules by monocyte/macrophages. Interestingly, MetS-lEVs, but not MetS-sEVs, increased SMC proliferation and IL-1ß production. EVs isolated from advanced human plaques demonstrated an accumulation of EVs carrying NLRP3 and their implication in endothelial permeability increase. Pharmacological inhibition of NLRP3-inflammasome carried by MetS-EVs prevented all the effects leading to vascular inflammation and remodeling. Conclusions Our data demonstrate that NLRP3-inflammasome, carried by EVs, is actively involved in vascular inflammation and atherosclerosis development in MetS. We highlight NLRP3 carried by EVs as potential biomarker and target for potential therapeutic strategies of atherosclerosis-related diseases leading to major adverse cardiovascular events. Graphical Abstract |
| format | Article |
| id | doaj-art-b9f2f51d4eae43e5be5437488aa785ae |
| institution | OA Journals |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | Cell Communication and Signaling |
| spelling | doaj-art-b9f2f51d4eae43e5be5437488aa785ae2025-08-20T02:07:40ZengBMCCell Communication and Signaling1478-811X2025-06-0123111910.1186/s12964-025-02296-8NLRP3, conveyed via extracellular vesicles from metabolic syndrome patients, is involved in atherosclerosis developmentXavier Vidal-Gómez0Luisa Vergori1Séverine Dubois2Frédéric Gagnadoux3Samir Henni4Reuben Veerapen5Olivier Meilhac6Mercedes Muñoz-Picos7Concepción Peiró8M. Carmen Martinez9Ramaroson Andriantsitohaina10on behalf of Metabol Study GroupPhyMedExp, University of Montpellier, INSERM, CNRSSOPAM, INSERM U1063, UNIV Angers, SFR ICATCHU d’AngersSOPAM, INSERM U1063, UNIV Angers, SFR ICATCHU d’AngersGroupe Clinifutur, Clinique Sainte-ClotildeDéTROI, INSERM U1188, Université de La RéunionSOPAM, INSERM U1063, UNIV Angers, SFR ICATDepartment of Pharmacology, Medicine School, Autonomous University of MadridPhyMedExp, University of Montpellier, INSERM, CNRSPhyMedExp, University of Montpellier, INSERM, CNRSAbstract Background Inappropriate activation of the Nod-like receptor protein 3 (NLRP3)-inflammasome contributes to atherosclerosis progression and plaque instability in patients with cardiovascular events. However, its role in the atherosclerosis is not fully understood. We sought to uncover actionable targets that could help to refine the diagnostic values of metabolic syndrome (MetS) patients by taking advantage of extracellular vesicles (EVs) to support the inflammatory hypothesis of atherosclerosis. Methods Circulating large (lEVs) and small (sEVs) EVs from non-MetS subjects and MetS patients were isolated and characterized. The involvement of NLRP3 in the effects of EVs on human aortic endothelial and smooth muscle cells (SMC) and macrophages were analyzed. The pathological relevance in human atherosclerotic lesions was investigated. Results Circulating levels of lEVs carrying NLRP3 correlated with metabolic risk factors associated with obesity and insulin resistance. Both types of EVs from MetS patients increased endothelial permeability, monocyte transmigration, SMC migration and secretion of pro-inflammatory molecules by monocyte/macrophages. Interestingly, MetS-lEVs, but not MetS-sEVs, increased SMC proliferation and IL-1ß production. EVs isolated from advanced human plaques demonstrated an accumulation of EVs carrying NLRP3 and their implication in endothelial permeability increase. Pharmacological inhibition of NLRP3-inflammasome carried by MetS-EVs prevented all the effects leading to vascular inflammation and remodeling. Conclusions Our data demonstrate that NLRP3-inflammasome, carried by EVs, is actively involved in vascular inflammation and atherosclerosis development in MetS. We highlight NLRP3 carried by EVs as potential biomarker and target for potential therapeutic strategies of atherosclerosis-related diseases leading to major adverse cardiovascular events. Graphical Abstracthttps://doi.org/10.1186/s12964-025-02296-8NLRP3Extracellular vesiclesMetabolic syndromeVascular inflammationAtherosclerosis development |
| spellingShingle | Xavier Vidal-Gómez Luisa Vergori Séverine Dubois Frédéric Gagnadoux Samir Henni Reuben Veerapen Olivier Meilhac Mercedes Muñoz-Picos Concepción Peiró M. Carmen Martinez Ramaroson Andriantsitohaina on behalf of Metabol Study Group NLRP3, conveyed via extracellular vesicles from metabolic syndrome patients, is involved in atherosclerosis development Cell Communication and Signaling NLRP3 Extracellular vesicles Metabolic syndrome Vascular inflammation Atherosclerosis development |
| title | NLRP3, conveyed via extracellular vesicles from metabolic syndrome patients, is involved in atherosclerosis development |
| title_full | NLRP3, conveyed via extracellular vesicles from metabolic syndrome patients, is involved in atherosclerosis development |
| title_fullStr | NLRP3, conveyed via extracellular vesicles from metabolic syndrome patients, is involved in atherosclerosis development |
| title_full_unstemmed | NLRP3, conveyed via extracellular vesicles from metabolic syndrome patients, is involved in atherosclerosis development |
| title_short | NLRP3, conveyed via extracellular vesicles from metabolic syndrome patients, is involved in atherosclerosis development |
| title_sort | nlrp3 conveyed via extracellular vesicles from metabolic syndrome patients is involved in atherosclerosis development |
| topic | NLRP3 Extracellular vesicles Metabolic syndrome Vascular inflammation Atherosclerosis development |
| url | https://doi.org/10.1186/s12964-025-02296-8 |
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