Transcriptomic profiling of thrombus-derived extracellular vesicles reveals PECAM-1 as a potential inflammatory marker for cardioembolic stroke patients
Accurate etiological diagnosis ensures appropriate secondary prevention of ischemic stroke (IS) patients. However, about 25–40% of IS cases remain of undetermined origin (referred to as ESUS if an unknown embolic source is suspected), highlighting the need to improve diagnostic precision. To identif...
| Autores: | , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad Pública de Navarra |
| Repositorio: | Academica-e. Repositorio Institucional de la Universidad Pública de Navarra |
| OAI Identifier: | oai:academica-e.unavarra.es:2454/55884 |
| Acceso en línea: | https://hdl.handle.net/2454/55884 |
| Access Level: | acceso abierto |
| Palabra clave: | Ischemic stroke Diagnostic Thrombus Extracellular vesicles Transcriptomes And inflammation related pathways |
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Transcriptomic profiling of thrombus-derived extracellular vesicles reveals PECAM-1 as a potential inflammatory marker for cardioembolic stroke patients |
| title |
Transcriptomic profiling of thrombus-derived extracellular vesicles reveals PECAM-1 as a potential inflammatory marker for cardioembolic stroke patients |
| spellingShingle |
Transcriptomic profiling of thrombus-derived extracellular vesicles reveals PECAM-1 as a potential inflammatory marker for cardioembolic stroke patients Machado, Florencio J.D. Ischemic stroke Diagnostic Thrombus Extracellular vesicles Transcriptomes And inflammation related pathways |
| title_short |
Transcriptomic profiling of thrombus-derived extracellular vesicles reveals PECAM-1 as a potential inflammatory marker for cardioembolic stroke patients |
| title_full |
Transcriptomic profiling of thrombus-derived extracellular vesicles reveals PECAM-1 as a potential inflammatory marker for cardioembolic stroke patients |
| title_fullStr |
Transcriptomic profiling of thrombus-derived extracellular vesicles reveals PECAM-1 as a potential inflammatory marker for cardioembolic stroke patients |
| title_full_unstemmed |
Transcriptomic profiling of thrombus-derived extracellular vesicles reveals PECAM-1 as a potential inflammatory marker for cardioembolic stroke patients |
| title_sort |
Transcriptomic profiling of thrombus-derived extracellular vesicles reveals PECAM-1 as a potential inflammatory marker for cardioembolic stroke patients |
| dc.creator.none.fl_str_mv |
Machado, Florencio J.D. Marta-Enguita, Juan Herrera, María Marta-Moreno, Javier Páramo, José A. Segura, Tomás Serrano-Heras, Gemma Hernández-Fernández, Francisco Arias-Salazar, Lourdes Yélamos-Sanz, Blanca Zandio, Beatriz Aymerich, Nuria Muñoz, Roberto Bermejo, Rebeca Roncal Mancho, Carmen Orbe, Josune |
| author |
Machado, Florencio J.D. |
| author_facet |
Machado, Florencio J.D. Marta-Enguita, Juan Herrera, María Marta-Moreno, Javier Páramo, José A. Segura, Tomás Serrano-Heras, Gemma Hernández-Fernández, Francisco Arias-Salazar, Lourdes Yélamos-Sanz, Blanca Zandio, Beatriz Aymerich, Nuria Muñoz, Roberto Bermejo, Rebeca Roncal Mancho, Carmen Orbe, Josune |
| author_role |
author |
| author2 |
Marta-Enguita, Juan Herrera, María Marta-Moreno, Javier Páramo, José A. Segura, Tomás Serrano-Heras, Gemma Hernández-Fernández, Francisco Arias-Salazar, Lourdes Yélamos-Sanz, Blanca Zandio, Beatriz Aymerich, Nuria Muñoz, Roberto Bermejo, Rebeca Roncal Mancho, Carmen Orbe, Josune |
| author2_role |
author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Ciencias de la Salud Osasun Zientziak |
| dc.subject.none.fl_str_mv |
Ischemic stroke Diagnostic Thrombus Extracellular vesicles Transcriptomes And inflammation related pathways |
| topic |
Ischemic stroke Diagnostic Thrombus Extracellular vesicles Transcriptomes And inflammation related pathways |
| description |
Accurate etiological diagnosis ensures appropriate secondary prevention of ischemic stroke (IS) patients. However, about 25–40% of IS cases remain of undetermined origin (referred to as ESUS if an unknown embolic source is suspected), highlighting the need to improve diagnostic precision. To identify potential biomarkers of IS etiologies, we analyzed the transcriptomic content of extracellular vesicles (EVs) from thrombi obtained after thrombectomy, including patients with cardioembolic (CE, n = 10), atherothrombotic (AT, n = 10) and ESUS (n = 10) IS (discovery cohort). mRNA levels of those differentially expressed genes in thrombus EVs were determined in microvascular brain endothelial cells after stimulation, revealing PECAM-1, as the most promising candidate. Next, PECAM-1 levels were determined in thrombi (n = 65) and serum samples (n = 95) of an independent validation cohort of IS patients, using immunohistochemistry and ELISA respectively. The transcriptome profiling and bioinformatics analysis revealed 1,514 gene transcripts in thrombus EVs, of which 114 were differentially expressed in AT vs CE etiologies. The genes upregulated in EVs from CE thrombi were enriched in pathways related to cell surface interactions at the vascular wall, leukocyte migration and neutrophil degranulation. Consistent with the increased PECAM-1 expression in thrombus EVs from CE vs AT etiologies, the endothelial expression of PECAM-1 increased after thrombin exposure and diminished upon atherogenic stimulation (oxLDL and TNFα). Moreover, thrombus expression of PECAM-1 was localized predominantly in platelet rich areas containing or surrounded by inflammatory cells and fibrin, and was higher in CE stroke thrombi. Serum levels of PECAM-1 were associated [OR (95%CI) 1.52 (1.14–2.03), p = 0.004] with the severity of stroke at Hospital admission. These findings collectively suggest that the transcriptional study of thrombus EVs may be useful to unravel the molecular pathways behind thrombus formation, and to explore local biological differences between IS etiologies. Specifically, PECAM-1, an adhesion molecule implicated in immuno-inflammatory processes, was increased in thrombi EVs and thrombi of patients with CE IS. Regarding the use of PECAM-1 as systemic biomarker, it did not discriminate IS etiologies, but was positively correlated with worse neurological outcome, suggesting a possible role of PECAM-1 in processes leading to brain injury post-IS. |
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2025 |
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2025 |
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Inglés |
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https://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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Transcriptomic profiling of thrombus-derived extracellular vesicles reveals PECAM-1 as a potential inflammatory marker for cardioembolic stroke patientsMachado, Florencio J.D.Marta-Enguita, JuanHerrera, MaríaMarta-Moreno, Javier Páramo, José A.Segura, TomásSerrano-Heras, GemmaHernández-Fernández, FranciscoArias-Salazar, LourdesYélamos-Sanz, BlancaZandio, BeatrizAymerich, NuriaMuñoz, RobertoBermejo, RebecaRoncal Mancho, CarmenOrbe, JosuneIschemic strokeDiagnosticThrombusExtracellular vesiclesTranscriptomesAnd inflammation related pathwaysAccurate etiological diagnosis ensures appropriate secondary prevention of ischemic stroke (IS) patients. However, about 25–40% of IS cases remain of undetermined origin (referred to as ESUS if an unknown embolic source is suspected), highlighting the need to improve diagnostic precision. To identify potential biomarkers of IS etiologies, we analyzed the transcriptomic content of extracellular vesicles (EVs) from thrombi obtained after thrombectomy, including patients with cardioembolic (CE, n = 10), atherothrombotic (AT, n = 10) and ESUS (n = 10) IS (discovery cohort). mRNA levels of those differentially expressed genes in thrombus EVs were determined in microvascular brain endothelial cells after stimulation, revealing PECAM-1, as the most promising candidate. Next, PECAM-1 levels were determined in thrombi (n = 65) and serum samples (n = 95) of an independent validation cohort of IS patients, using immunohistochemistry and ELISA respectively. The transcriptome profiling and bioinformatics analysis revealed 1,514 gene transcripts in thrombus EVs, of which 114 were differentially expressed in AT vs CE etiologies. The genes upregulated in EVs from CE thrombi were enriched in pathways related to cell surface interactions at the vascular wall, leukocyte migration and neutrophil degranulation. Consistent with the increased PECAM-1 expression in thrombus EVs from CE vs AT etiologies, the endothelial expression of PECAM-1 increased after thrombin exposure and diminished upon atherogenic stimulation (oxLDL and TNFα). Moreover, thrombus expression of PECAM-1 was localized predominantly in platelet rich areas containing or surrounded by inflammatory cells and fibrin, and was higher in CE stroke thrombi. Serum levels of PECAM-1 were associated [OR (95%CI) 1.52 (1.14–2.03), p = 0.004] with the severity of stroke at Hospital admission. These findings collectively suggest that the transcriptional study of thrombus EVs may be useful to unravel the molecular pathways behind thrombus formation, and to explore local biological differences between IS etiologies. Specifically, PECAM-1, an adhesion molecule implicated in immuno-inflammatory processes, was increased in thrombi EVs and thrombi of patients with CE IS. Regarding the use of PECAM-1 as systemic biomarker, it did not discriminate IS etiologies, but was positively correlated with worse neurological outcome, suggesting a possible role of PECAM-1 in processes leading to brain injury post-IS.Red de Investigación Cooperativa Orientada a Resultados en Salud-Enfermedades Vasculares Cerebrales (RICORS-Ictus) RD21/0006/0008, RD24/0009/0028, and PI22/00436 financiado por el Instituto de Salud Carlos III, "Cofinanciado por la Unión Europea".BMCCiencias de la SaludOsasun Zientziak2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/vnd.ms-powerpointhttps://hdl.handle.net/2454/55884reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarrainstname:Universidad Pública de NavarraInglésinfo:eu-repo/grantAgreement/ISCIII//RD21%2F0006%2F0008info:eu-repo/grantAgreement/ISCIII//RD24%2F0009%2F0028info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica, Técnica y de Innovación 2021-2023/PI22%2F00436© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:academica-e.unavarra.es:2454/558842026-06-17T12:41:47Z |
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