Resolvin E1 attenuates doxorubicin-induced endothelial senescence by modulating NLRP3 inflammasome activation
Endothelial cell senescence contributes to chronic inflammation and endothelial dysfunction, while favoring cardiovascular disorders and frailty. Senescent cells acquire a pro-inflammatory secretory phenotype that further propagates inflammation and senescence to neighboring cells. Cell senescence c...
| Autores: | , , , , , , , , |
|---|---|
| Formato: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Recursos: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/710495 |
| Acesso em linha: | http://hdl.handle.net/10486/710495 https://dx.doi.org/10.1016/j.bcp.2022.115078 |
| Access Level: | acceso abierto |
| Palavra-chave: | Resolvin E1 endothelial senescence NLRP3 inflammasome doxorubicin interleukin 1β vascular aging Medicina |
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Resolvin E1 attenuates doxorubicin-induced endothelial senescence by modulating NLRP3 inflammasome activationShamoon, LiciaEspitia-Corredor, Jenaro A.Dongil, PilarMenéndez Ribes, MartaRomero, AlejandraValencia Fernández, InésDíaz-Araya, GuillermoSánchez Ferrer, Carlos FélixPeiró Vallejo, M. ConcepciónResolvin E1endothelial senescenceNLRP3 inflammasomedoxorubicininterleukin 1βvascular agingMedicinaEndothelial cell senescence contributes to chronic inflammation and endothelial dysfunction, while favoring cardiovascular disorders and frailty. Senescent cells acquire a pro-inflammatory secretory phenotype that further propagates inflammation and senescence to neighboring cells. Cell senescence can be provoked by plethora of stressors, including inflammatory molecules and chemotherapeutic drugs. Doxorubicin (Doxo) is a powerful anthracycline anticancer drug whose clinical application is constrained by a dose-limiting cardiovascular toxicity. We here investigated whether cell senescence can contribute to the vascular damage elicited by Doxo. In human umbilical vein endothelial cells (HUVEC) cultures, Doxo (10–100 nM) increased the number of SA-β-gal positive cells and the levels of γH2AX, p21 and p53, used as markers of senescence. Moreover, we identified Doxo-induced senescence to be mediated by the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome, a key player of the immune innate system capable of releasing interleukin (IL)-1β. In fact, IL-1β itself mimicked the stimulatory action of Doxo on both NLRP3 activation and cellular senescence, while the pharmacological blockade of IL-1 receptors markedly attenuated the pro-senescence effects of Doxo. In search of additional pharmacological strategies to attenuate Doxo-induced endothelial senescence, we identified resolvin E1 (RvE1), an endogenous pro-resolving mediator, as capable of reducing cell senescence induced by both Doxo and IL-1β by interfering with the increased expression of pP65, NLRP3, and pro-IL-1β proteins and with the formation of active NLRP3 inflammasome complexes. Overall, RvE1 and the blockade of the NLRP3 inflammasome-IL-1β axis may offer a novel therapeutic approach against Doxo-induced cardiovascular toxicity and subsequent sequelaeElsevierDepartamento de FarmacologíaFacultad de Medicina20222022-05-10research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/710495https://dx.doi.org/10.1016/j.bcp.2022.115078reponame: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:10486/7104952026-06-23T12:46:27Z |
| dc.title.none.fl_str_mv |
Resolvin E1 attenuates doxorubicin-induced endothelial senescence by modulating NLRP3 inflammasome activation |
| title |
Resolvin E1 attenuates doxorubicin-induced endothelial senescence by modulating NLRP3 inflammasome activation |
| spellingShingle |
Resolvin E1 attenuates doxorubicin-induced endothelial senescence by modulating NLRP3 inflammasome activation Shamoon, Licia Resolvin E1 endothelial senescence NLRP3 inflammasome doxorubicin interleukin 1β vascular aging Medicina |
| title_short |
Resolvin E1 attenuates doxorubicin-induced endothelial senescence by modulating NLRP3 inflammasome activation |
| title_full |
Resolvin E1 attenuates doxorubicin-induced endothelial senescence by modulating NLRP3 inflammasome activation |
| title_fullStr |
Resolvin E1 attenuates doxorubicin-induced endothelial senescence by modulating NLRP3 inflammasome activation |
| title_full_unstemmed |
Resolvin E1 attenuates doxorubicin-induced endothelial senescence by modulating NLRP3 inflammasome activation |
| title_sort |
Resolvin E1 attenuates doxorubicin-induced endothelial senescence by modulating NLRP3 inflammasome activation |
| dc.creator.none.fl_str_mv |
Shamoon, Licia Espitia-Corredor, Jenaro A. Dongil, Pilar Menéndez Ribes, Marta Romero, Alejandra Valencia Fernández, Inés Díaz-Araya, Guillermo Sánchez Ferrer, Carlos Félix Peiró Vallejo, M. Concepción |
| author |
Shamoon, Licia |
| author_facet |
Shamoon, Licia Espitia-Corredor, Jenaro A. Dongil, Pilar Menéndez Ribes, Marta Romero, Alejandra Valencia Fernández, Inés Díaz-Araya, Guillermo Sánchez Ferrer, Carlos Félix Peiró Vallejo, M. Concepción |
| author_role |
author |
| author2 |
Espitia-Corredor, Jenaro A. Dongil, Pilar Menéndez Ribes, Marta Romero, Alejandra Valencia Fernández, Inés Díaz-Araya, Guillermo Sánchez Ferrer, Carlos Félix Peiró Vallejo, M. Concepción |
| author2_role |
author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamento de Farmacología Facultad de Medicina |
| dc.subject.none.fl_str_mv |
Resolvin E1 endothelial senescence NLRP3 inflammasome doxorubicin interleukin 1β vascular aging Medicina |
| topic |
Resolvin E1 endothelial senescence NLRP3 inflammasome doxorubicin interleukin 1β vascular aging Medicina |
| description |
Endothelial cell senescence contributes to chronic inflammation and endothelial dysfunction, while favoring cardiovascular disorders and frailty. Senescent cells acquire a pro-inflammatory secretory phenotype that further propagates inflammation and senescence to neighboring cells. Cell senescence can be provoked by plethora of stressors, including inflammatory molecules and chemotherapeutic drugs. Doxorubicin (Doxo) is a powerful anthracycline anticancer drug whose clinical application is constrained by a dose-limiting cardiovascular toxicity. We here investigated whether cell senescence can contribute to the vascular damage elicited by Doxo. In human umbilical vein endothelial cells (HUVEC) cultures, Doxo (10–100 nM) increased the number of SA-β-gal positive cells and the levels of γH2AX, p21 and p53, used as markers of senescence. Moreover, we identified Doxo-induced senescence to be mediated by the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome, a key player of the immune innate system capable of releasing interleukin (IL)-1β. In fact, IL-1β itself mimicked the stimulatory action of Doxo on both NLRP3 activation and cellular senescence, while the pharmacological blockade of IL-1 receptors markedly attenuated the pro-senescence effects of Doxo. In search of additional pharmacological strategies to attenuate Doxo-induced endothelial senescence, we identified resolvin E1 (RvE1), an endogenous pro-resolving mediator, as capable of reducing cell senescence induced by both Doxo and IL-1β by interfering with the increased expression of pP65, NLRP3, and pro-IL-1β proteins and with the formation of active NLRP3 inflammasome complexes. Overall, RvE1 and the blockade of the NLRP3 inflammasome-IL-1β axis may offer a novel therapeutic approach against Doxo-induced cardiovascular toxicity and subsequent sequelae |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2022-05-10 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 AM http://purl.org/coar/version/c_ab4af688f83e57aa |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10486/710495 https://dx.doi.org/10.1016/j.bcp.2022.115078 |
| url |
http://hdl.handle.net/10486/710495 https://dx.doi.org/10.1016/j.bcp.2022.115078 |
| 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 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
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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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