Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosis

Autores
Quintar, Amado Alfredo; McArdle, Sara; Wolf, Dennis; Marki, Alex; Ehinger, Erik; Vassallo, Melanie; Miller, Jacqueline; Mikulski, Zbigniew; Ley, Klaus Friedrich; Buscher, Konrad
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Non-classical mouse monocyte (CX3CR1, Ly-6C) patrolling along the vessels of the microcirculation is critical for endothelial homeostasis and inflammation. Due to technical challenges it is currently not established how patrolling occurs in large arteries. OBJECTIVE:: This study was undertaken to elucidate the molecular, migratory and functional phenotype of patrolling monocytes in the high shear and pulsatile environment of large arteries in healthy, hyperlipidemic and atherosclerotic conditions. METHODS AND RESULTS:: Applying a new method for stable, long-term two-photon intravital microscopy of unrestrained large arteries in live CX3CR1-GFP mice, we show that non-classical monocytes patrol inside healthy carotid arteries at a velocity of 36 μm/min, three times faster than in microvessels. The tracks are less straight but lead preferentially downstream. The number of patrolling monocytes is increased 9-fold by feeding wildtype mice a western diet or by applying topical TLR7/8 agonists. A similar increase is seen in CX3CR1/apoE mice on chow diet, with a further 2-3-fold increase on western diet (22-fold over healthy). In plaque conditions, monocytes are readily captured onto the endothelium from free flow. Stable patrolling is unaffected in CX3CR1-deficient mice and involves the contribution of LFA-1 and α4 integrins. The endothelial damage in atherosclerotic carotid arteries was assessed by electron microscopy and correlates with the number of intraluminal patrollers. Abolishing patrolling monocytes in Nr4a1 apoE mice leads to pronounced endothelial apoptosis. CONCLUSIONS:: Arterial patrolling is a prominent new feature of non-classical monocytes with unique molecular and kinetic properties. It is highly upregulated in hyperlipidemia and atherosclerosis in an CX3CR1-independent fashion, and plays a potential role in endothelial protection.Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.
Fil: Quintar, Amado Alfredo. La Jolla Institute for Allergy and Immunology; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: McArdle, Sara. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Wolf, Dennis. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Marki, Alex. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Ehinger, Erik. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Vassallo, Melanie. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Miller, Jacqueline. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Mikulski, Zbigniew. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Ley, Klaus Friedrich. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Buscher, Konrad. La Jolla Institute for Allergy and Immunology; Estados Unidos
Materia
PATROLLING MONOCYTES
ATHEROSCLEROSIS
ENDOTHELIUM
LIVE IMAGING
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:11336/57885

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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosisQuintar, Amado AlfredoMcArdle, SaraWolf, DennisMarki, AlexEhinger, ErikVassallo, MelanieMiller, JacquelineMikulski, ZbigniewLey, Klaus FriedrichBuscher, KonradPATROLLING MONOCYTESATHEROSCLEROSISENDOTHELIUMLIVE IMAGINGhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Non-classical mouse monocyte (CX3CR1, Ly-6C) patrolling along the vessels of the microcirculation is critical for endothelial homeostasis and inflammation. Due to technical challenges it is currently not established how patrolling occurs in large arteries. OBJECTIVE:: This study was undertaken to elucidate the molecular, migratory and functional phenotype of patrolling monocytes in the high shear and pulsatile environment of large arteries in healthy, hyperlipidemic and atherosclerotic conditions. METHODS AND RESULTS:: Applying a new method for stable, long-term two-photon intravital microscopy of unrestrained large arteries in live CX3CR1-GFP mice, we show that non-classical monocytes patrol inside healthy carotid arteries at a velocity of 36 μm/min, three times faster than in microvessels. The tracks are less straight but lead preferentially downstream. The number of patrolling monocytes is increased 9-fold by feeding wildtype mice a western diet or by applying topical TLR7/8 agonists. A similar increase is seen in CX3CR1/apoE mice on chow diet, with a further 2-3-fold increase on western diet (22-fold over healthy). In plaque conditions, monocytes are readily captured onto the endothelium from free flow. Stable patrolling is unaffected in CX3CR1-deficient mice and involves the contribution of LFA-1 and α4 integrins. The endothelial damage in atherosclerotic carotid arteries was assessed by electron microscopy and correlates with the number of intraluminal patrollers. Abolishing patrolling monocytes in Nr4a1 apoE mice leads to pronounced endothelial apoptosis. CONCLUSIONS:: Arterial patrolling is a prominent new feature of non-classical monocytes with unique molecular and kinetic properties. It is highly upregulated in hyperlipidemia and atherosclerosis in an CX3CR1-independent fashion, and plays a potential role in endothelial protection.Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.Fil: Quintar, Amado Alfredo. La Jolla Institute for Allergy and Immunology; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: McArdle, Sara. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Wolf, Dennis. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Marki, Alex. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Ehinger, Erik. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Vassallo, Melanie. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Miller, Jacqueline. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Mikulski, Zbigniew. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Ley, Klaus Friedrich. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Buscher, Konrad. La Jolla Institute for Allergy and Immunology; Estados UnidosLippincott Williams2017-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/57885Quintar, Amado Alfredo; McArdle, Sara; Wolf, Dennis; Marki, Alex; Ehinger, Erik; et al.; Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosis; Lippincott Williams; Circulation Research; 120; 11; 3-2017; 1789-17990009-73301524-4571CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1161/CIRCRESAHA.117.310739info:eu-repo/semantics/altIdentifier/url/https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.117.310739info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:23:12Zoai:ri.conicet.gov.ar:11336/57885instacron: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:34982025-09-29 10:23:12.973CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosis
title Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosis
spellingShingle Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosis
Quintar, Amado Alfredo
PATROLLING MONOCYTES
ATHEROSCLEROSIS
ENDOTHELIUM
LIVE IMAGING
title_short Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosis
title_full Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosis
title_fullStr Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosis
title_full_unstemmed Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosis
title_sort Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosis
dc.creator.none.fl_str_mv Quintar, Amado Alfredo
McArdle, Sara
Wolf, Dennis
Marki, Alex
Ehinger, Erik
Vassallo, Melanie
Miller, Jacqueline
Mikulski, Zbigniew
Ley, Klaus Friedrich
Buscher, Konrad
author Quintar, Amado Alfredo
author_facet Quintar, Amado Alfredo
McArdle, Sara
Wolf, Dennis
Marki, Alex
Ehinger, Erik
Vassallo, Melanie
Miller, Jacqueline
Mikulski, Zbigniew
Ley, Klaus Friedrich
Buscher, Konrad
author_role author
author2 McArdle, Sara
Wolf, Dennis
Marki, Alex
Ehinger, Erik
Vassallo, Melanie
Miller, Jacqueline
Mikulski, Zbigniew
Ley, Klaus Friedrich
Buscher, Konrad
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PATROLLING MONOCYTES
ATHEROSCLEROSIS
ENDOTHELIUM
LIVE IMAGING
topic PATROLLING MONOCYTES
ATHEROSCLEROSIS
ENDOTHELIUM
LIVE IMAGING
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Non-classical mouse monocyte (CX3CR1, Ly-6C) patrolling along the vessels of the microcirculation is critical for endothelial homeostasis and inflammation. Due to technical challenges it is currently not established how patrolling occurs in large arteries. OBJECTIVE:: This study was undertaken to elucidate the molecular, migratory and functional phenotype of patrolling monocytes in the high shear and pulsatile environment of large arteries in healthy, hyperlipidemic and atherosclerotic conditions. METHODS AND RESULTS:: Applying a new method for stable, long-term two-photon intravital microscopy of unrestrained large arteries in live CX3CR1-GFP mice, we show that non-classical monocytes patrol inside healthy carotid arteries at a velocity of 36 μm/min, three times faster than in microvessels. The tracks are less straight but lead preferentially downstream. The number of patrolling monocytes is increased 9-fold by feeding wildtype mice a western diet or by applying topical TLR7/8 agonists. A similar increase is seen in CX3CR1/apoE mice on chow diet, with a further 2-3-fold increase on western diet (22-fold over healthy). In plaque conditions, monocytes are readily captured onto the endothelium from free flow. Stable patrolling is unaffected in CX3CR1-deficient mice and involves the contribution of LFA-1 and α4 integrins. The endothelial damage in atherosclerotic carotid arteries was assessed by electron microscopy and correlates with the number of intraluminal patrollers. Abolishing patrolling monocytes in Nr4a1 apoE mice leads to pronounced endothelial apoptosis. CONCLUSIONS:: Arterial patrolling is a prominent new feature of non-classical monocytes with unique molecular and kinetic properties. It is highly upregulated in hyperlipidemia and atherosclerosis in an CX3CR1-independent fashion, and plays a potential role in endothelial protection.Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.
Fil: Quintar, Amado Alfredo. La Jolla Institute for Allergy and Immunology; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: McArdle, Sara. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Wolf, Dennis. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Marki, Alex. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Ehinger, Erik. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Vassallo, Melanie. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Miller, Jacqueline. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Mikulski, Zbigniew. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Ley, Klaus Friedrich. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Buscher, Konrad. La Jolla Institute for Allergy and Immunology; Estados Unidos
description Non-classical mouse monocyte (CX3CR1, Ly-6C) patrolling along the vessels of the microcirculation is critical for endothelial homeostasis and inflammation. Due to technical challenges it is currently not established how patrolling occurs in large arteries. OBJECTIVE:: This study was undertaken to elucidate the molecular, migratory and functional phenotype of patrolling monocytes in the high shear and pulsatile environment of large arteries in healthy, hyperlipidemic and atherosclerotic conditions. METHODS AND RESULTS:: Applying a new method for stable, long-term two-photon intravital microscopy of unrestrained large arteries in live CX3CR1-GFP mice, we show that non-classical monocytes patrol inside healthy carotid arteries at a velocity of 36 μm/min, three times faster than in microvessels. The tracks are less straight but lead preferentially downstream. The number of patrolling monocytes is increased 9-fold by feeding wildtype mice a western diet or by applying topical TLR7/8 agonists. A similar increase is seen in CX3CR1/apoE mice on chow diet, with a further 2-3-fold increase on western diet (22-fold over healthy). In plaque conditions, monocytes are readily captured onto the endothelium from free flow. Stable patrolling is unaffected in CX3CR1-deficient mice and involves the contribution of LFA-1 and α4 integrins. The endothelial damage in atherosclerotic carotid arteries was assessed by electron microscopy and correlates with the number of intraluminal patrollers. Abolishing patrolling monocytes in Nr4a1 apoE mice leads to pronounced endothelial apoptosis. CONCLUSIONS:: Arterial patrolling is a prominent new feature of non-classical monocytes with unique molecular and kinetic properties. It is highly upregulated in hyperlipidemia and atherosclerosis in an CX3CR1-independent fashion, and plays a potential role in endothelial protection.Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.
publishDate 2017
dc.date.none.fl_str_mv 2017-03
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/11336/57885
Quintar, Amado Alfredo; McArdle, Sara; Wolf, Dennis; Marki, Alex; Ehinger, Erik; et al.; Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosis; Lippincott Williams; Circulation Research; 120; 11; 3-2017; 1789-1799
0009-7330
1524-4571
CONICET Digital
CONICET
url http://hdl.handle.net/11336/57885
identifier_str_mv Quintar, Amado Alfredo; McArdle, Sara; Wolf, Dennis; Marki, Alex; Ehinger, Erik; et al.; Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosis; Lippincott Williams; Circulation Research; 120; 11; 3-2017; 1789-1799
0009-7330
1524-4571
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1161/CIRCRESAHA.117.310739
info:eu-repo/semantics/altIdentifier/url/https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.117.310739
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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