Interferon-stimulated gene 15 pathway is a novel mediator of endothelial dysfunction and aneurysms development in angiotensin II infused mice through increased oxidative stress
Aims: Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that induces a reversible post-translational modification (ISGylation) and can also be secreted as a free form. ISG15 plays an essential role as host-defence response to microbial infection; however, its contribution to vas...
| Autores: | , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Recursos: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/113240 |
| Acesso em linha: | https://hdl.handle.net/10171/113240 |
| Access Level: | acceso abierto |
| Palavra-chave: | Endothelial dysfunction ISG15 Inflammation Oxidative stress Vascular remodelling |
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Interferon-stimulated gene 15 pathway is a novel mediator of endothelial dysfunction and aneurysms development in angiotensin II infused mice through increased oxidative stressGonzález-Amor, M. (María)|||/items/8aac613d-7677-49e5-8b1d-10aaa81cce95García-Redondo, A.B. (Ana B.)|||/items/011a7d46-dea7-4be2-b083-cb5a6d2d1f64Jorge, I. (Inmaculada)|||/items/651e3189-e21e-460c-9671-bee0237fe0d9Zalba-Goñi, G. (Guillermo)|||/items/71410fa2-baa5-4efc-bce7-14b4b0e23802Becares, M. (Martina)|||/items/4bef4dfb-e712-4c11-842a-aa604802be8cRuiz-Rodríguez, M.J. (María J.)|||/items/6ff22309-2863-4f8b-936b-699f14ccd00fRodriguez, C. (Cristina)|||/items/e32601ac-8006-4e12-a425-f29e83e5123bBermeo, H. (Hugo)|||/items/e53ada5b-b7e9-48a0-9ee8-2686834c02f4Rodrigues-Díez, R. (Raquel)|||/items/1776a27c-0097-4a6d-a2d8-9da49e508107Rios, F.J. ( Francisco J.)|||/items/bd3f33c6-a45e-42df-b1c8-b8a41e0991d7Montezano, A.C. (Augusto C.)|||/items/8cd238a2-2b3e-437e-a72f-6279de203caaMartinez-Gonzalez, J. (José)|||/items/ff293a5b-8c80-46b5-a432-648b0fbe392cVázquez, J. (Jesús)|||/items/2103692d-1fe1-4fa5-a429-2988182aa3d0Redondo, J.M. (Juan Miguel)|||/items/cae3cfa4-0e3e-4042-a6c1-8a97ac164242Touyz, R.M. (Rhian M.)|||/items/d5c2fb35-3de0-4fa0-872a-c0e7b0d21095Guerra, S. (Susana)|||/items/b5e433aa-267d-464c-bf61-1e8de9028fe0Salaices, M. (Mercedes)|||/items/33dc2371-8e01-4545-9e9f-b1afe32d7755Briones, A.M. (Ana M.)|||/items/24bda785-74f7-404f-a00e-e97b50ccbe67Endothelial dysfunctionISG15InflammationOxidative stressVascular remodellingAims: Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that induces a reversible post-translational modification (ISGylation) and can also be secreted as a free form. ISG15 plays an essential role as host-defence response to microbial infection; however, its contribution to vascular damage associated with hypertension is unknown. Methods and results: Bioinformatics identified ISG15 as a mediator of hypertension-associated vascular damage. ISG15 expression positively correlated with systolic and diastolic blood pressure and carotid intima-media thickness in human peripheral blood mononuclear cells. Consistently, Isg15 expression was enhanced in aorta from hypertension models and in angiotensin II (AngII)-treated vascular cells and macrophages. Proteomics revealed differential expression of proteins implicated in cardiovascular function, extracellular matrix and remodelling, and vascular redox state in aorta from AngII-infused ISG15-/- mice. Moreover, ISG15-/- mice were protected against AngII-induced hypertension, vascular stiffness, elastin remodelling, endothelial dysfunction, and expression of inflammatory and oxidative stress markers. Conversely, mice with excessive ISGylation (USP18C61A) show enhanced AngII-induced hypertension, vascular fibrosis, inflammation and reactive oxygen species (ROS) generation along with elastin breaks, aortic dilation, and rupture. Accordingly, human and murine abdominal aortic aneurysms showed augmented ISG15 expression. Mechanistically, ISG15 induces vascular ROS production, while antioxidant treatment prevented ISG15-induced endothelial dysfunction and vascular remodelling. Conclusion: ISG15 is a novel mediator of vascular damage in hypertension through oxidative stress and inflammation.Oxford University PressDadun. Depósito Académico Digital Universidad de Navarra20222022-01-0120222022-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/113240reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/1132402026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Interferon-stimulated gene 15 pathway is a novel mediator of endothelial dysfunction and aneurysms development in angiotensin II infused mice through increased oxidative stress |
| title |
Interferon-stimulated gene 15 pathway is a novel mediator of endothelial dysfunction and aneurysms development in angiotensin II infused mice through increased oxidative stress |
| spellingShingle |
Interferon-stimulated gene 15 pathway is a novel mediator of endothelial dysfunction and aneurysms development in angiotensin II infused mice through increased oxidative stress González-Amor, M. (María)|||/items/8aac613d-7677-49e5-8b1d-10aaa81cce95 Endothelial dysfunction ISG15 Inflammation Oxidative stress Vascular remodelling |
| title_short |
Interferon-stimulated gene 15 pathway is a novel mediator of endothelial dysfunction and aneurysms development in angiotensin II infused mice through increased oxidative stress |
| title_full |
Interferon-stimulated gene 15 pathway is a novel mediator of endothelial dysfunction and aneurysms development in angiotensin II infused mice through increased oxidative stress |
| title_fullStr |
Interferon-stimulated gene 15 pathway is a novel mediator of endothelial dysfunction and aneurysms development in angiotensin II infused mice through increased oxidative stress |
| title_full_unstemmed |
Interferon-stimulated gene 15 pathway is a novel mediator of endothelial dysfunction and aneurysms development in angiotensin II infused mice through increased oxidative stress |
| title_sort |
Interferon-stimulated gene 15 pathway is a novel mediator of endothelial dysfunction and aneurysms development in angiotensin II infused mice through increased oxidative stress |
| dc.creator.none.fl_str_mv |
González-Amor, M. (María)|||/items/8aac613d-7677-49e5-8b1d-10aaa81cce95 García-Redondo, A.B. (Ana B.)|||/items/011a7d46-dea7-4be2-b083-cb5a6d2d1f64 Jorge, I. (Inmaculada)|||/items/651e3189-e21e-460c-9671-bee0237fe0d9 Zalba-Goñi, G. (Guillermo)|||/items/71410fa2-baa5-4efc-bce7-14b4b0e23802 Becares, M. (Martina)|||/items/4bef4dfb-e712-4c11-842a-aa604802be8c Ruiz-Rodríguez, M.J. (María J.)|||/items/6ff22309-2863-4f8b-936b-699f14ccd00f Rodriguez, C. (Cristina)|||/items/e32601ac-8006-4e12-a425-f29e83e5123b Bermeo, H. (Hugo)|||/items/e53ada5b-b7e9-48a0-9ee8-2686834c02f4 Rodrigues-Díez, R. (Raquel)|||/items/1776a27c-0097-4a6d-a2d8-9da49e508107 Rios, F.J. ( Francisco J.)|||/items/bd3f33c6-a45e-42df-b1c8-b8a41e0991d7 Montezano, A.C. (Augusto C.)|||/items/8cd238a2-2b3e-437e-a72f-6279de203caa Martinez-Gonzalez, J. (José)|||/items/ff293a5b-8c80-46b5-a432-648b0fbe392c Vázquez, J. (Jesús)|||/items/2103692d-1fe1-4fa5-a429-2988182aa3d0 Redondo, J.M. (Juan Miguel)|||/items/cae3cfa4-0e3e-4042-a6c1-8a97ac164242 Touyz, R.M. (Rhian M.)|||/items/d5c2fb35-3de0-4fa0-872a-c0e7b0d21095 Guerra, S. (Susana)|||/items/b5e433aa-267d-464c-bf61-1e8de9028fe0 Salaices, M. (Mercedes)|||/items/33dc2371-8e01-4545-9e9f-b1afe32d7755 Briones, A.M. (Ana M.)|||/items/24bda785-74f7-404f-a00e-e97b50ccbe67 |
| author |
González-Amor, M. (María)|||/items/8aac613d-7677-49e5-8b1d-10aaa81cce95 |
| author_facet |
González-Amor, M. (María)|||/items/8aac613d-7677-49e5-8b1d-10aaa81cce95 García-Redondo, A.B. (Ana B.)|||/items/011a7d46-dea7-4be2-b083-cb5a6d2d1f64 Jorge, I. (Inmaculada)|||/items/651e3189-e21e-460c-9671-bee0237fe0d9 Zalba-Goñi, G. (Guillermo)|||/items/71410fa2-baa5-4efc-bce7-14b4b0e23802 Becares, M. (Martina)|||/items/4bef4dfb-e712-4c11-842a-aa604802be8c Ruiz-Rodríguez, M.J. (María J.)|||/items/6ff22309-2863-4f8b-936b-699f14ccd00f Rodriguez, C. (Cristina)|||/items/e32601ac-8006-4e12-a425-f29e83e5123b Bermeo, H. (Hugo)|||/items/e53ada5b-b7e9-48a0-9ee8-2686834c02f4 Rodrigues-Díez, R. (Raquel)|||/items/1776a27c-0097-4a6d-a2d8-9da49e508107 Rios, F.J. ( Francisco J.)|||/items/bd3f33c6-a45e-42df-b1c8-b8a41e0991d7 Montezano, A.C. (Augusto C.)|||/items/8cd238a2-2b3e-437e-a72f-6279de203caa Martinez-Gonzalez, J. (José)|||/items/ff293a5b-8c80-46b5-a432-648b0fbe392c Vázquez, J. (Jesús)|||/items/2103692d-1fe1-4fa5-a429-2988182aa3d0 Redondo, J.M. (Juan Miguel)|||/items/cae3cfa4-0e3e-4042-a6c1-8a97ac164242 Touyz, R.M. (Rhian M.)|||/items/d5c2fb35-3de0-4fa0-872a-c0e7b0d21095 Guerra, S. (Susana)|||/items/b5e433aa-267d-464c-bf61-1e8de9028fe0 Salaices, M. (Mercedes)|||/items/33dc2371-8e01-4545-9e9f-b1afe32d7755 Briones, A.M. (Ana M.)|||/items/24bda785-74f7-404f-a00e-e97b50ccbe67 |
| author_role |
author |
| author2 |
García-Redondo, A.B. (Ana B.)|||/items/011a7d46-dea7-4be2-b083-cb5a6d2d1f64 Jorge, I. (Inmaculada)|||/items/651e3189-e21e-460c-9671-bee0237fe0d9 Zalba-Goñi, G. (Guillermo)|||/items/71410fa2-baa5-4efc-bce7-14b4b0e23802 Becares, M. (Martina)|||/items/4bef4dfb-e712-4c11-842a-aa604802be8c Ruiz-Rodríguez, M.J. (María J.)|||/items/6ff22309-2863-4f8b-936b-699f14ccd00f Rodriguez, C. (Cristina)|||/items/e32601ac-8006-4e12-a425-f29e83e5123b Bermeo, H. (Hugo)|||/items/e53ada5b-b7e9-48a0-9ee8-2686834c02f4 Rodrigues-Díez, R. (Raquel)|||/items/1776a27c-0097-4a6d-a2d8-9da49e508107 Rios, F.J. ( Francisco J.)|||/items/bd3f33c6-a45e-42df-b1c8-b8a41e0991d7 Montezano, A.C. (Augusto C.)|||/items/8cd238a2-2b3e-437e-a72f-6279de203caa Martinez-Gonzalez, J. (José)|||/items/ff293a5b-8c80-46b5-a432-648b0fbe392c Vázquez, J. (Jesús)|||/items/2103692d-1fe1-4fa5-a429-2988182aa3d0 Redondo, J.M. (Juan Miguel)|||/items/cae3cfa4-0e3e-4042-a6c1-8a97ac164242 Touyz, R.M. (Rhian M.)|||/items/d5c2fb35-3de0-4fa0-872a-c0e7b0d21095 Guerra, S. (Susana)|||/items/b5e433aa-267d-464c-bf61-1e8de9028fe0 Salaices, M. (Mercedes)|||/items/33dc2371-8e01-4545-9e9f-b1afe32d7755 Briones, A.M. (Ana M.)|||/items/24bda785-74f7-404f-a00e-e97b50ccbe67 |
| 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 |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Endothelial dysfunction ISG15 Inflammation Oxidative stress Vascular remodelling |
| topic |
Endothelial dysfunction ISG15 Inflammation Oxidative stress Vascular remodelling |
| description |
Aims: Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that induces a reversible post-translational modification (ISGylation) and can also be secreted as a free form. ISG15 plays an essential role as host-defence response to microbial infection; however, its contribution to vascular damage associated with hypertension is unknown. Methods and results: Bioinformatics identified ISG15 as a mediator of hypertension-associated vascular damage. ISG15 expression positively correlated with systolic and diastolic blood pressure and carotid intima-media thickness in human peripheral blood mononuclear cells. Consistently, Isg15 expression was enhanced in aorta from hypertension models and in angiotensin II (AngII)-treated vascular cells and macrophages. Proteomics revealed differential expression of proteins implicated in cardiovascular function, extracellular matrix and remodelling, and vascular redox state in aorta from AngII-infused ISG15-/- mice. Moreover, ISG15-/- mice were protected against AngII-induced hypertension, vascular stiffness, elastin remodelling, endothelial dysfunction, and expression of inflammatory and oxidative stress markers. Conversely, mice with excessive ISGylation (USP18C61A) show enhanced AngII-induced hypertension, vascular fibrosis, inflammation and reactive oxygen species (ROS) generation along with elastin breaks, aortic dilation, and rupture. Accordingly, human and murine abdominal aortic aneurysms showed augmented ISG15 expression. Mechanistically, ISG15 induces vascular ROS production, while antioxidant treatment prevented ISG15-induced endothelial dysfunction and vascular remodelling. Conclusion: ISG15 is a novel mediator of vascular damage in hypertension through oxidative stress and inflammation. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2022-01-01 2022 2022-01-01 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/113240 |
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https://hdl.handle.net/10171/113240 |
| dc.language.none.fl_str_mv |
Inglés eng |
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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 |
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Oxford University Press |
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Oxford University Press |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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1869424771671785472 |
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15,81155 |