Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunctionwithout affecting blood pressure in angiotensin II-high salt-induced hypertension

Autores
González, Germán Esteban; Rhaleb, Nour Eddine; D'Ambrosio, Martin A.; Nakagawa, Pablo; Liu, Yunhe; Leung, Pablo; Dai, Xiangguo; Yang, Xiao Ping; Peterson, Edward L.; Carretero, Oscar A.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objective: Inflammation has been proposed as a key component in the development of hypertension and cardiac remodeling associated with different cardiovascular diseases. However, the role of the proinflammatory cytokine interleukin-6 in the chronic stage of hypertension is not well defined. Here, we tested the hypothesis that deletion of interleukin-6 protects against the development of hypertension, cardiac inflammation, fibrosis, remodeling and dysfunction induced by high salt diet and angiotensin II (Ang II). Methods: Male C57BL/6J and interleukin-6-knock out (KO) mice were implanted with telemetry devices for blood pressure (BP) measurements, fed a 4% NaCl diet, and infused with either vehicle or Ang II (90 ng/min per mouse subcutaneously) for 8 weeks. We studied BP and cardiac function by echocardiography at baseline, 4 and 8 weeks. Results: Myocyte cross-sectional area (MCSA), macrophage infiltration, and myocardial fibrosis were also assessed. BP increased similarly in both strains when treated with Ang II and high salt (Ang II-high salt); however, C57BL/6J mice developed a more severe decrease in left ventricle ejection fraction, fibrosis, and macrophage infiltration compared with interleukin-6-KO mice. No differences between strains were observed in MCSA, capillary density and MCSA to capillary density ratio. Conclusion: In conclusion, absence of interleukin -6 did not alter the development of Ang II-high salt-induced hypertension and cardiac hypertrophy, but it prevented the development of cardiac dysfunction, myocardial inflammation, and fibrosis. This indicates that interleukin-6 plays an important role in hypertensive heart damage but not in the development of hypertension.
Fil: González, Germán Esteban. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Henry Ford Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rhaleb, Nour Eddine. Henry Ford Hospital; Estados Unidos
Fil: D'Ambrosio, Martin A.. Henry Ford Hospital; Estados Unidos
Fil: Nakagawa, Pablo. Henry Ford Hospital; Estados Unidos
Fil: Liu, Yunhe. Henry Ford Hospital; Estados Unidos
Fil: Leung, Pablo. Henry Ford Hospital; Estados Unidos
Fil: Dai, Xiangguo. Henry Ford Hospital; Estados Unidos
Fil: Yang, Xiao Ping. Henry Ford Hospital; Estados Unidos. Wayne State University; Estados Unidos
Fil: Peterson, Edward L.. Henry Ford Hospital; Estados Unidos
Fil: Carretero, Oscar A.. Henry Ford Hospital; Estados Unidos
Materia
ANGIOTENSIN II
HEART FAILURE
HYPERTENSION
INTERLEUKIN 6
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/98221
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/98221
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunctionwithout affecting blood pressure in angiotensin II-high salt-induced hypertensionGonzález, Germán EstebanRhaleb, Nour EddineD'Ambrosio, Martin A.Nakagawa, PabloLiu, YunheLeung, PabloDai, XiangguoYang, Xiao PingPeterson, Edward L.Carretero, Oscar A.ANGIOTENSIN IIHEART FAILUREHYPERTENSIONINTERLEUKIN 6https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Objective: Inflammation has been proposed as a key component in the development of hypertension and cardiac remodeling associated with different cardiovascular diseases. However, the role of the proinflammatory cytokine interleukin-6 in the chronic stage of hypertension is not well defined. Here, we tested the hypothesis that deletion of interleukin-6 protects against the development of hypertension, cardiac inflammation, fibrosis, remodeling and dysfunction induced by high salt diet and angiotensin II (Ang II). Methods: Male C57BL/6J and interleukin-6-knock out (KO) mice were implanted with telemetry devices for blood pressure (BP) measurements, fed a 4% NaCl diet, and infused with either vehicle or Ang II (90 ng/min per mouse subcutaneously) for 8 weeks. We studied BP and cardiac function by echocardiography at baseline, 4 and 8 weeks. Results: Myocyte cross-sectional area (MCSA), macrophage infiltration, and myocardial fibrosis were also assessed. BP increased similarly in both strains when treated with Ang II and high salt (Ang II-high salt); however, C57BL/6J mice developed a more severe decrease in left ventricle ejection fraction, fibrosis, and macrophage infiltration compared with interleukin-6-KO mice. No differences between strains were observed in MCSA, capillary density and MCSA to capillary density ratio. Conclusion: In conclusion, absence of interleukin -6 did not alter the development of Ang II-high salt-induced hypertension and cardiac hypertrophy, but it prevented the development of cardiac dysfunction, myocardial inflammation, and fibrosis. This indicates that interleukin-6 plays an important role in hypertensive heart damage but not in the development of hypertension.Fil: González, Germán Esteban. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Henry Ford Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rhaleb, Nour Eddine. Henry Ford Hospital; Estados UnidosFil: D'Ambrosio, Martin A.. Henry Ford Hospital; Estados UnidosFil: Nakagawa, Pablo. Henry Ford Hospital; Estados UnidosFil: Liu, Yunhe. Henry Ford Hospital; Estados UnidosFil: Leung, Pablo. Henry Ford Hospital; Estados UnidosFil: Dai, Xiangguo. Henry Ford Hospital; Estados UnidosFil: Yang, Xiao Ping. Henry Ford Hospital; Estados Unidos. Wayne State University; Estados UnidosFil: Peterson, Edward L.. Henry Ford Hospital; Estados UnidosFil: Carretero, Oscar A.. Henry Ford Hospital; Estados UnidosLippincott Williams2015-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/98221González, Germán Esteban; Rhaleb, Nour Eddine; D'Ambrosio, Martin A.; Nakagawa, Pablo; Liu, Yunhe; et al.; Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunctionwithout affecting blood pressure in angiotensin II-high salt-induced hypertension; Lippincott Williams; Journal of Hypertension; 33; 1; 1-2015; 144-1520263-6352CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1097/HJH.0000000000000358info:eu-repo/semantics/altIdentifier/url/https://insights.ovid.com/article/00004872-201501000-00018info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:50:02Zoai:ri.conicet.gov.ar:11336/98221instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:50:02.385CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunctionwithout affecting blood pressure in angiotensin II-high salt-induced hypertension
title Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunctionwithout affecting blood pressure in angiotensin II-high salt-induced hypertension
spellingShingle Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunctionwithout affecting blood pressure in angiotensin II-high salt-induced hypertension
González, Germán Esteban
ANGIOTENSIN II
HEART FAILURE
HYPERTENSION
INTERLEUKIN 6
title_short Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunctionwithout affecting blood pressure in angiotensin II-high salt-induced hypertension
title_full Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunctionwithout affecting blood pressure in angiotensin II-high salt-induced hypertension
title_fullStr Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunctionwithout affecting blood pressure in angiotensin II-high salt-induced hypertension
title_full_unstemmed Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunctionwithout affecting blood pressure in angiotensin II-high salt-induced hypertension
title_sort Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunctionwithout affecting blood pressure in angiotensin II-high salt-induced hypertension
dc.creator.none.fl_str_mv González, Germán Esteban
Rhaleb, Nour Eddine
D'Ambrosio, Martin A.
Nakagawa, Pablo
Liu, Yunhe
Leung, Pablo
Dai, Xiangguo
Yang, Xiao Ping
Peterson, Edward L.
Carretero, Oscar A.
author González, Germán Esteban
author_facet González, Germán Esteban
Rhaleb, Nour Eddine
D'Ambrosio, Martin A.
Nakagawa, Pablo
Liu, Yunhe
Leung, Pablo
Dai, Xiangguo
Yang, Xiao Ping
Peterson, Edward L.
Carretero, Oscar A.
author_role author
author2 Rhaleb, Nour Eddine
D'Ambrosio, Martin A.
Nakagawa, Pablo
Liu, Yunhe
Leung, Pablo
Dai, Xiangguo
Yang, Xiao Ping
Peterson, Edward L.
Carretero, Oscar A.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANGIOTENSIN II
HEART FAILURE
HYPERTENSION
INTERLEUKIN 6
topic ANGIOTENSIN II
HEART FAILURE
HYPERTENSION
INTERLEUKIN 6
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objective: Inflammation has been proposed as a key component in the development of hypertension and cardiac remodeling associated with different cardiovascular diseases. However, the role of the proinflammatory cytokine interleukin-6 in the chronic stage of hypertension is not well defined. Here, we tested the hypothesis that deletion of interleukin-6 protects against the development of hypertension, cardiac inflammation, fibrosis, remodeling and dysfunction induced by high salt diet and angiotensin II (Ang II). Methods: Male C57BL/6J and interleukin-6-knock out (KO) mice were implanted with telemetry devices for blood pressure (BP) measurements, fed a 4% NaCl diet, and infused with either vehicle or Ang II (90 ng/min per mouse subcutaneously) for 8 weeks. We studied BP and cardiac function by echocardiography at baseline, 4 and 8 weeks. Results: Myocyte cross-sectional area (MCSA), macrophage infiltration, and myocardial fibrosis were also assessed. BP increased similarly in both strains when treated with Ang II and high salt (Ang II-high salt); however, C57BL/6J mice developed a more severe decrease in left ventricle ejection fraction, fibrosis, and macrophage infiltration compared with interleukin-6-KO mice. No differences between strains were observed in MCSA, capillary density and MCSA to capillary density ratio. Conclusion: In conclusion, absence of interleukin -6 did not alter the development of Ang II-high salt-induced hypertension and cardiac hypertrophy, but it prevented the development of cardiac dysfunction, myocardial inflammation, and fibrosis. This indicates that interleukin-6 plays an important role in hypertensive heart damage but not in the development of hypertension.
Fil: González, Germán Esteban. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Henry Ford Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rhaleb, Nour Eddine. Henry Ford Hospital; Estados Unidos
Fil: D'Ambrosio, Martin A.. Henry Ford Hospital; Estados Unidos
Fil: Nakagawa, Pablo. Henry Ford Hospital; Estados Unidos
Fil: Liu, Yunhe. Henry Ford Hospital; Estados Unidos
Fil: Leung, Pablo. Henry Ford Hospital; Estados Unidos
Fil: Dai, Xiangguo. Henry Ford Hospital; Estados Unidos
Fil: Yang, Xiao Ping. Henry Ford Hospital; Estados Unidos. Wayne State University; Estados Unidos
Fil: Peterson, Edward L.. Henry Ford Hospital; Estados Unidos
Fil: Carretero, Oscar A.. Henry Ford Hospital; Estados Unidos
description Objective: Inflammation has been proposed as a key component in the development of hypertension and cardiac remodeling associated with different cardiovascular diseases. However, the role of the proinflammatory cytokine interleukin-6 in the chronic stage of hypertension is not well defined. Here, we tested the hypothesis that deletion of interleukin-6 protects against the development of hypertension, cardiac inflammation, fibrosis, remodeling and dysfunction induced by high salt diet and angiotensin II (Ang II). Methods: Male C57BL/6J and interleukin-6-knock out (KO) mice were implanted with telemetry devices for blood pressure (BP) measurements, fed a 4% NaCl diet, and infused with either vehicle or Ang II (90 ng/min per mouse subcutaneously) for 8 weeks. We studied BP and cardiac function by echocardiography at baseline, 4 and 8 weeks. Results: Myocyte cross-sectional area (MCSA), macrophage infiltration, and myocardial fibrosis were also assessed. BP increased similarly in both strains when treated with Ang II and high salt (Ang II-high salt); however, C57BL/6J mice developed a more severe decrease in left ventricle ejection fraction, fibrosis, and macrophage infiltration compared with interleukin-6-KO mice. No differences between strains were observed in MCSA, capillary density and MCSA to capillary density ratio. Conclusion: In conclusion, absence of interleukin -6 did not alter the development of Ang II-high salt-induced hypertension and cardiac hypertrophy, but it prevented the development of cardiac dysfunction, myocardial inflammation, and fibrosis. This indicates that interleukin-6 plays an important role in hypertensive heart damage but not in the development of hypertension.
publishDate 2015
dc.date.none.fl_str_mv 2015-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/98221
González, Germán Esteban; Rhaleb, Nour Eddine; D'Ambrosio, Martin A.; Nakagawa, Pablo; Liu, Yunhe; et al.; Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunctionwithout affecting blood pressure in angiotensin II-high salt-induced hypertension; Lippincott Williams; Journal of Hypertension; 33; 1; 1-2015; 144-152
0263-6352
CONICET Digital
CONICET
url http://hdl.handle.net/11336/98221
identifier_str_mv González, Germán Esteban; Rhaleb, Nour Eddine; D'Ambrosio, Martin A.; Nakagawa, Pablo; Liu, Yunhe; et al.; Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunctionwithout affecting blood pressure in angiotensin II-high salt-induced hypertension; Lippincott Williams; Journal of Hypertension; 33; 1; 1-2015; 144-152
0263-6352
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1097/HJH.0000000000000358
info:eu-repo/semantics/altIdentifier/url/https://insights.ovid.com/article/00004872-201501000-00018
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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