Complement C5 protein as a marker of subclinical atherosclerosis
Background: The mechanisms underlying early atherosclerotic plaque formation are not completely understood. Moreover, plasma biomarkers of subclinical atherosclerosis are lacking. Objectives: The purpose of this study was to analyze the temporal and topologically resolved protein changes taking plac...
| Autores: | , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/693219 |
| Acceso en línea: | http://hdl.handle.net/10486/693219 https://dx.doi.org/10.1016/j.jacc.2020.02.058 |
| Access Level: | acceso abierto |
| Palabra clave: | Biomarkers Complement system Proteomics Subclinical atherosclerosis Medicina |
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Complement C5 protein as a marker of subclinical atherosclerosisMartínez-López, DiegoRoldán-Montero, RaquelGarcía-Marqués, FernandoNúñez, EstefaníaJorge, InmaculadaCamafeita, EmilioMínguez, PabloRodriguez de Córdoba, SantiagoLópez-Melgar, BeatrizLara-Pezzi, EnriqueFernández-Ortiz, AntonioIbáñez, BorjaValdivielso, José ManuelFuster Carulla, ValentíMichel, Jean-BaptisteBlanco-Colio, Luis MiguelVázquez, JesúsMartín Ventura, José LuisBiomarkersComplement systemProteomicsSubclinical atherosclerosisMedicinaBackground: The mechanisms underlying early atherosclerotic plaque formation are not completely understood. Moreover, plasma biomarkers of subclinical atherosclerosis are lacking. Objectives: The purpose of this study was to analyze the temporal and topologically resolved protein changes taking place in human aortas with early atherosclerosis to find new potential diagnostic and/or therapeutic targets. Methods: The protein composition of healthy aortas (media layer) or with early atheroma (fatty streak and fibrolipidic, media and intima layers) was analyzed by deep quantitative multiplexed proteomics. Further analysis was performed by Western blot, immunohistochemistry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. Plasma levels of complement C5 were analyzed in relation to the presence of generalized (>2 plaques) or incipient (0 to 2 plaques) subclinical atherosclerosis in 2 independent clinical cohorts (PESA [Progression of Early Subclinical Atherosclerosis] [n = 360] and NEFRONA [National Observatory of Atherosclerosis in Nephrology] [n = 394]). Results: Proteins involved in lipid transport, complement system, immunoglobulin superfamily, and hemostasis are increased in early plaques. Components from the complement activation pathway were predominantly increased in the intima of fibrolipidic plaques. Among them, increased C5 protein levels were further confirmed by Western blot, enzyme-linked immunosorbent assay and immunohistochemistry, and associated with in situ complement activation. Plasma C5 was significantly increased in individuals with generalized subclinical atherosclerosis in both PESA and NEFRONA cohorts, independently of risk factors. Moreover, in the PESA study, C5 plasma levels positively correlated with global plaque volume and coronary calcification. Conclusions: Activation of the complement system is a major alteration in early atherosclerotic plaques and is reflected by increased C5 plasma levels, which have promising value as a novel circulating biomarker of subclinical atherosclerosisElsevier Inc.Departamento de MedicinaFacultad de Medicina20202020-04-28research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/693219https://dx.doi.org/10.1016/j.jacc.2020.02.058reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6932192026-06-23T12:46:27Z |
| dc.title.none.fl_str_mv |
Complement C5 protein as a marker of subclinical atherosclerosis |
| title |
Complement C5 protein as a marker of subclinical atherosclerosis |
| spellingShingle |
Complement C5 protein as a marker of subclinical atherosclerosis Martínez-López, Diego Biomarkers Complement system Proteomics Subclinical atherosclerosis Medicina |
| title_short |
Complement C5 protein as a marker of subclinical atherosclerosis |
| title_full |
Complement C5 protein as a marker of subclinical atherosclerosis |
| title_fullStr |
Complement C5 protein as a marker of subclinical atherosclerosis |
| title_full_unstemmed |
Complement C5 protein as a marker of subclinical atherosclerosis |
| title_sort |
Complement C5 protein as a marker of subclinical atherosclerosis |
| dc.creator.none.fl_str_mv |
Martínez-López, Diego Roldán-Montero, Raquel García-Marqués, Fernando Núñez, Estefanía Jorge, Inmaculada Camafeita, Emilio Mínguez, Pablo Rodriguez de Córdoba, Santiago López-Melgar, Beatriz Lara-Pezzi, Enrique Fernández-Ortiz, Antonio Ibáñez, Borja Valdivielso, José Manuel Fuster Carulla, Valentí Michel, Jean-Baptiste Blanco-Colio, Luis Miguel Vázquez, Jesús Martín Ventura, José Luis |
| author |
Martínez-López, Diego |
| author_facet |
Martínez-López, Diego Roldán-Montero, Raquel García-Marqués, Fernando Núñez, Estefanía Jorge, Inmaculada Camafeita, Emilio Mínguez, Pablo Rodriguez de Córdoba, Santiago López-Melgar, Beatriz Lara-Pezzi, Enrique Fernández-Ortiz, Antonio Ibáñez, Borja Valdivielso, José Manuel Fuster Carulla, Valentí Michel, Jean-Baptiste Blanco-Colio, Luis Miguel Vázquez, Jesús Martín Ventura, José Luis |
| author_role |
author |
| author2 |
Roldán-Montero, Raquel García-Marqués, Fernando Núñez, Estefanía Jorge, Inmaculada Camafeita, Emilio Mínguez, Pablo Rodriguez de Córdoba, Santiago López-Melgar, Beatriz Lara-Pezzi, Enrique Fernández-Ortiz, Antonio Ibáñez, Borja Valdivielso, José Manuel Fuster Carulla, Valentí Michel, Jean-Baptiste Blanco-Colio, Luis Miguel Vázquez, Jesús Martín Ventura, José Luis |
| author2_role |
author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamento de Medicina Facultad de Medicina |
| dc.subject.none.fl_str_mv |
Biomarkers Complement system Proteomics Subclinical atherosclerosis Medicina |
| topic |
Biomarkers Complement system Proteomics Subclinical atherosclerosis Medicina |
| description |
Background: The mechanisms underlying early atherosclerotic plaque formation are not completely understood. Moreover, plasma biomarkers of subclinical atherosclerosis are lacking. Objectives: The purpose of this study was to analyze the temporal and topologically resolved protein changes taking place in human aortas with early atherosclerosis to find new potential diagnostic and/or therapeutic targets. Methods: The protein composition of healthy aortas (media layer) or with early atheroma (fatty streak and fibrolipidic, media and intima layers) was analyzed by deep quantitative multiplexed proteomics. Further analysis was performed by Western blot, immunohistochemistry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. Plasma levels of complement C5 were analyzed in relation to the presence of generalized (>2 plaques) or incipient (0 to 2 plaques) subclinical atherosclerosis in 2 independent clinical cohorts (PESA [Progression of Early Subclinical Atherosclerosis] [n = 360] and NEFRONA [National Observatory of Atherosclerosis in Nephrology] [n = 394]). Results: Proteins involved in lipid transport, complement system, immunoglobulin superfamily, and hemostasis are increased in early plaques. Components from the complement activation pathway were predominantly increased in the intima of fibrolipidic plaques. Among them, increased C5 protein levels were further confirmed by Western blot, enzyme-linked immunosorbent assay and immunohistochemistry, and associated with in situ complement activation. Plasma C5 was significantly increased in individuals with generalized subclinical atherosclerosis in both PESA and NEFRONA cohorts, independently of risk factors. Moreover, in the PESA study, C5 plasma levels positively correlated with global plaque volume and coronary calcification. Conclusions: Activation of the complement system is a major alteration in early atherosclerotic plaques and is reflected by increased C5 plasma levels, which have promising value as a novel circulating biomarker of subclinical atherosclerosis |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020-04-28 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10486/693219 https://dx.doi.org/10.1016/j.jacc.2020.02.058 |
| url |
http://hdl.handle.net/10486/693219 https://dx.doi.org/10.1016/j.jacc.2020.02.058 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier Inc. |
| publisher.none.fl_str_mv |
Elsevier Inc. |
| dc.source.none.fl_str_mv |
reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid |
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Universidad Autónoma de Madrid |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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15.301603 |