Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor y 2 in Mice

Autores: Stachon, Peter; Geis, Serjosha; Peikert, Alexander; Heidenreich, Adrian; Anto Michel, Nathaly; Üenal, Fatih; Hoppe, Natalie; Dufner, Bianca; Schulte, Lisa; Marchini, Timoteo Oscar; Cicko, Sanja; Korcan Ayata, Cemil; Zech, Andreas; Wolf, Dennis; Hilgendorf, Ingo; Willecke, Florian; Reinöhl, Jochen; von zur Muhlen, Constantin; Bode, Christoph; Idzko, Marco; Zirlik, Andreas
Año de publicación: 2016
Idioma: inglés
Tipo de recurso: artículo
Estado: versión publicada
Descripción: Objective - A solid body of evidence supports a role of extracellular ATP and its P2 receptors in innate and adaptive immunity. It promotes inflammation as a danger signal in various chronic inflammatory diseases. Thus, we hypothesize contribution of extracellular ATP and its receptor P2Y 2 in vascular inflammation and atherosclerosis. Approach and Results - Extracellular ATP induced leukocyte rolling, adhesion, and migration in vivo as assessed by intravital microscopy and in sterile peritonitis. To test the role of extracellular ATP in atherosclerosis, ATP or saline as control was injected intraperitoneally 3× a week in low-density lipoprotein receptor -/- mice consuming high cholesterol diet. Atherosclerosis significantly increased after 16 weeks in ATP-treated mice (n=13; control group, 0.26 mm2; ATP group, 0.33 mm2; P=0.01). To gain into the role of ATP-receptor P2Y 2 in ATP-induced leukocyte recruitment, ATP was administered systemically in P2Y 2 -deficient or P2Y 2 -competent mice. In P2Y 2 -deficient mice, the ATP-induced leukocyte adhesion was significantly reduced as assessed by intravital microscopy. P2Y 2 expression in atherosclerosis was measured by real-time polymerase chain reaction and immunohistochemistry and demonstrates an increased expression mainly caused by influx of P2Y 2 -expressing macrophages. To investigate the functional role of P2Y 2 in atherogenesis, P2Y 2 -deficient low-density lipoprotein receptor -/- mice consumed high cholesterol diet. After 16 weeks, P2Y 2 -deficient mice showed significantly reduced atherosclerotic lesions with decreased macrophages compared with P2Y 2 -competent mice (n=11; aortic arch: control group, 0.25 mm 2; P2Y 2 -deficient, 0.14 mm2; P=0.04). Mechanistically, atherosclerotic lesions from P2Y 2 -deficient mice expressed less vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 RNA. Conclusions - We show that extracellular ATP induces vascular inflammation and atherosclerosis via activation of P2Y 2.
Fil: Stachon, Peter. Albert Ludwigs University of Freiburg; Alemania
Fil: Geis, Serjosha. Albert Ludwigs University of Freiburg; Alemania
Fil: Peikert, Alexander. Albert Ludwigs University of Freiburg; Alemania
Fil: Heidenreich, Adrian. Albert Ludwigs University of Freiburg; Alemania
Fil: Anto Michel, Nathaly. Albert Ludwigs University of Freiburg; Alemania
Fil: Üenal, Fatih. Albert Ludwigs University of Freiburg; Alemania
Fil: Hoppe, Natalie. Albert Ludwigs University of Freiburg; Alemania
Fil: Dufner, Bianca. Albert Ludwigs University of Freiburg; Alemania
Fil: Schulte, Lisa. Albert Ludwigs University of Freiburg; Alemania
Fil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Cicko, Sanja. Albert Ludwigs University of Freiburg; Alemania
Fil: Korcan Ayata, Cemil. Albert Ludwigs University of Freiburg; Alemania
Fil: Zech, Andreas. Albert Ludwigs University of Freiburg; Alemania
Fil: Wolf, Dennis. Albert Ludwigs University of Freiburg; Alemania
Fil: Hilgendorf, Ingo. Albert Ludwigs University of Freiburg; Alemania
Fil: Willecke, Florian. Albert Ludwigs University of Freiburg; Alemania
Fil: Reinöhl, Jochen. Albert Ludwigs University of Freiburg; Alemania
Fil: von zur Muhlen, Constantin. Albert Ludwigs University of Freiburg; Alemania
Fil: Bode, Christoph. Albert Ludwigs University of Freiburg; Alemania
Fil: Idzko, Marco. Albert Ludwigs University of Freiburg; Alemania
Fil: Zirlik, Andreas. Albert Ludwigs University of Freiburg; Alemania
Materia: ADENOSINE TRIPHOSPHATE
ATHEROSCLEROSIS
IMMUNITY
LEUKOCYTES
MICE
RECEPTORS, PURINERGIC P2Y2
Nivel de accesibilidad: acceso abierto
Condiciones de uso: https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
Institución: Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador: oai:ri.conicet.gov.ar:11336/151541

Acceder

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network_acronym_str	CONICETDig
repository_id_str	3498
network_name_str	CONICET Digital (CONICET)
spelling	Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor y 2 in MiceStachon, PeterGeis, SerjoshaPeikert, AlexanderHeidenreich, AdrianAnto Michel, NathalyÜenal, FatihHoppe, NatalieDufner, BiancaSchulte, LisaMarchini, Timoteo OscarCicko, SanjaKorcan Ayata, CemilZech, AndreasWolf, DennisHilgendorf, IngoWillecke, FlorianReinöhl, Jochenvon zur Muhlen, ConstantinBode, ChristophIdzko, MarcoZirlik, AndreasADENOSINE TRIPHOSPHATEATHEROSCLEROSISIMMUNITYLEUKOCYTESMICERECEPTORS, PURINERGIC P2Y2https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Objective - A solid body of evidence supports a role of extracellular ATP and its P2 receptors in innate and adaptive immunity. It promotes inflammation as a danger signal in various chronic inflammatory diseases. Thus, we hypothesize contribution of extracellular ATP and its receptor P2Y 2 in vascular inflammation and atherosclerosis. Approach and Results - Extracellular ATP induced leukocyte rolling, adhesion, and migration in vivo as assessed by intravital microscopy and in sterile peritonitis. To test the role of extracellular ATP in atherosclerosis, ATP or saline as control was injected intraperitoneally 3× a week in low-density lipoprotein receptor -/- mice consuming high cholesterol diet. Atherosclerosis significantly increased after 16 weeks in ATP-treated mice (n=13; control group, 0.26 mm2; ATP group, 0.33 mm2; P=0.01). To gain into the role of ATP-receptor P2Y 2 in ATP-induced leukocyte recruitment, ATP was administered systemically in P2Y 2 -deficient or P2Y 2 -competent mice. In P2Y 2 -deficient mice, the ATP-induced leukocyte adhesion was significantly reduced as assessed by intravital microscopy. P2Y 2 expression in atherosclerosis was measured by real-time polymerase chain reaction and immunohistochemistry and demonstrates an increased expression mainly caused by influx of P2Y 2 -expressing macrophages. To investigate the functional role of P2Y 2 in atherogenesis, P2Y 2 -deficient low-density lipoprotein receptor -/- mice consumed high cholesterol diet. After 16 weeks, P2Y 2 -deficient mice showed significantly reduced atherosclerotic lesions with decreased macrophages compared with P2Y 2 -competent mice (n=11; aortic arch: control group, 0.25 mm 2; P2Y 2 -deficient, 0.14 mm2; P=0.04). Mechanistically, atherosclerotic lesions from P2Y 2 -deficient mice expressed less vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 RNA. Conclusions - We show that extracellular ATP induces vascular inflammation and atherosclerosis via activation of P2Y 2.Fil: Stachon, Peter. Albert Ludwigs University of Freiburg; AlemaniaFil: Geis, Serjosha. Albert Ludwigs University of Freiburg; AlemaniaFil: Peikert, Alexander. Albert Ludwigs University of Freiburg; AlemaniaFil: Heidenreich, Adrian. Albert Ludwigs University of Freiburg; AlemaniaFil: Anto Michel, Nathaly. Albert Ludwigs University of Freiburg; AlemaniaFil: Üenal, Fatih. Albert Ludwigs University of Freiburg; AlemaniaFil: Hoppe, Natalie. Albert Ludwigs University of Freiburg; AlemaniaFil: Dufner, Bianca. Albert Ludwigs University of Freiburg; AlemaniaFil: Schulte, Lisa. Albert Ludwigs University of Freiburg; AlemaniaFil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Cicko, Sanja. Albert Ludwigs University of Freiburg; AlemaniaFil: Korcan Ayata, Cemil. Albert Ludwigs University of Freiburg; AlemaniaFil: Zech, Andreas. Albert Ludwigs University of Freiburg; AlemaniaFil: Wolf, Dennis. Albert Ludwigs University of Freiburg; AlemaniaFil: Hilgendorf, Ingo. Albert Ludwigs University of Freiburg; AlemaniaFil: Willecke, Florian. Albert Ludwigs University of Freiburg; AlemaniaFil: Reinöhl, Jochen. Albert Ludwigs University of Freiburg; AlemaniaFil: von zur Muhlen, Constantin. Albert Ludwigs University of Freiburg; AlemaniaFil: Bode, Christoph. Albert Ludwigs University of Freiburg; AlemaniaFil: Idzko, Marco. Albert Ludwigs University of Freiburg; AlemaniaFil: Zirlik, Andreas. Albert Ludwigs University of Freiburg; AlemaniaLippincott Williams2016-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/151541Stachon, Peter; Geis, Serjosha; Peikert, Alexander; Heidenreich, Adrian; Anto Michel, Nathaly; et al.; Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor y 2 in Mice; Lippincott Williams; Arteriosclerosis, Thrombosis, and Vascular Biology; 36; 8; 8-2016; 1577-15861079-5642CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1161/ATVBAHA.115.307397info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:58:00Zoai:ri.conicet.gov.ar:11336/151541instacron: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 09:58:01.206CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv	Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor y 2 in Mice
title	Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor y 2 in Mice
spellingShingle	Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor y 2 in Mice Stachon, Peter ADENOSINE TRIPHOSPHATE ATHEROSCLEROSIS IMMUNITY LEUKOCYTES MICE RECEPTORS, PURINERGIC P2Y2
title_short	Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor y 2 in Mice
title_full	Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor y 2 in Mice
title_fullStr	Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor y 2 in Mice
title_full_unstemmed	Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor y 2 in Mice
title_sort	Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor y 2 in Mice
dc.creator.none.fl_str_mv	Stachon, Peter Geis, Serjosha Peikert, Alexander Heidenreich, Adrian Anto Michel, Nathaly Üenal, Fatih Hoppe, Natalie Dufner, Bianca Schulte, Lisa Marchini, Timoteo Oscar Cicko, Sanja Korcan Ayata, Cemil Zech, Andreas Wolf, Dennis Hilgendorf, Ingo Willecke, Florian Reinöhl, Jochen von zur Muhlen, Constantin Bode, Christoph Idzko, Marco Zirlik, Andreas
author	Stachon, Peter
author_facet	Stachon, Peter Geis, Serjosha Peikert, Alexander Heidenreich, Adrian Anto Michel, Nathaly Üenal, Fatih Hoppe, Natalie Dufner, Bianca Schulte, Lisa Marchini, Timoteo Oscar Cicko, Sanja Korcan Ayata, Cemil Zech, Andreas Wolf, Dennis Hilgendorf, Ingo Willecke, Florian Reinöhl, Jochen von zur Muhlen, Constantin Bode, Christoph Idzko, Marco Zirlik, Andreas
author_role	author
author2	Geis, Serjosha Peikert, Alexander Heidenreich, Adrian Anto Michel, Nathaly Üenal, Fatih Hoppe, Natalie Dufner, Bianca Schulte, Lisa Marchini, Timoteo Oscar Cicko, Sanja Korcan Ayata, Cemil Zech, Andreas Wolf, Dennis Hilgendorf, Ingo Willecke, Florian Reinöhl, Jochen von zur Muhlen, Constantin Bode, Christoph Idzko, Marco Zirlik, Andreas
author2_role	author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	ADENOSINE TRIPHOSPHATE ATHEROSCLEROSIS IMMUNITY LEUKOCYTES MICE RECEPTORS, PURINERGIC P2Y2
topic	ADENOSINE TRIPHOSPHATE ATHEROSCLEROSIS IMMUNITY LEUKOCYTES MICE RECEPTORS, PURINERGIC P2Y2
purl_subject.fl_str_mv	https://purl.org/becyt/ford/3.2 https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv	Objective - A solid body of evidence supports a role of extracellular ATP and its P2 receptors in innate and adaptive immunity. It promotes inflammation as a danger signal in various chronic inflammatory diseases. Thus, we hypothesize contribution of extracellular ATP and its receptor P2Y 2 in vascular inflammation and atherosclerosis. Approach and Results - Extracellular ATP induced leukocyte rolling, adhesion, and migration in vivo as assessed by intravital microscopy and in sterile peritonitis. To test the role of extracellular ATP in atherosclerosis, ATP or saline as control was injected intraperitoneally 3× a week in low-density lipoprotein receptor -/- mice consuming high cholesterol diet. Atherosclerosis significantly increased after 16 weeks in ATP-treated mice (n=13; control group, 0.26 mm2; ATP group, 0.33 mm2; P=0.01). To gain into the role of ATP-receptor P2Y 2 in ATP-induced leukocyte recruitment, ATP was administered systemically in P2Y 2 -deficient or P2Y 2 -competent mice. In P2Y 2 -deficient mice, the ATP-induced leukocyte adhesion was significantly reduced as assessed by intravital microscopy. P2Y 2 expression in atherosclerosis was measured by real-time polymerase chain reaction and immunohistochemistry and demonstrates an increased expression mainly caused by influx of P2Y 2 -expressing macrophages. To investigate the functional role of P2Y 2 in atherogenesis, P2Y 2 -deficient low-density lipoprotein receptor -/- mice consumed high cholesterol diet. After 16 weeks, P2Y 2 -deficient mice showed significantly reduced atherosclerotic lesions with decreased macrophages compared with P2Y 2 -competent mice (n=11; aortic arch: control group, 0.25 mm 2; P2Y 2 -deficient, 0.14 mm2; P=0.04). Mechanistically, atherosclerotic lesions from P2Y 2 -deficient mice expressed less vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 RNA. Conclusions - We show that extracellular ATP induces vascular inflammation and atherosclerosis via activation of P2Y 2. Fil: Stachon, Peter. Albert Ludwigs University of Freiburg; Alemania Fil: Geis, Serjosha. Albert Ludwigs University of Freiburg; Alemania Fil: Peikert, Alexander. Albert Ludwigs University of Freiburg; Alemania Fil: Heidenreich, Adrian. Albert Ludwigs University of Freiburg; Alemania Fil: Anto Michel, Nathaly. Albert Ludwigs University of Freiburg; Alemania Fil: Üenal, Fatih. Albert Ludwigs University of Freiburg; Alemania Fil: Hoppe, Natalie. Albert Ludwigs University of Freiburg; Alemania Fil: Dufner, Bianca. Albert Ludwigs University of Freiburg; Alemania Fil: Schulte, Lisa. Albert Ludwigs University of Freiburg; Alemania Fil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina Fil: Cicko, Sanja. Albert Ludwigs University of Freiburg; Alemania Fil: Korcan Ayata, Cemil. Albert Ludwigs University of Freiburg; Alemania Fil: Zech, Andreas. Albert Ludwigs University of Freiburg; Alemania Fil: Wolf, Dennis. Albert Ludwigs University of Freiburg; Alemania Fil: Hilgendorf, Ingo. Albert Ludwigs University of Freiburg; Alemania Fil: Willecke, Florian. Albert Ludwigs University of Freiburg; Alemania Fil: Reinöhl, Jochen. Albert Ludwigs University of Freiburg; Alemania Fil: von zur Muhlen, Constantin. Albert Ludwigs University of Freiburg; Alemania Fil: Bode, Christoph. Albert Ludwigs University of Freiburg; Alemania Fil: Idzko, Marco. Albert Ludwigs University of Freiburg; Alemania Fil: Zirlik, Andreas. Albert Ludwigs University of Freiburg; Alemania
description	Objective - A solid body of evidence supports a role of extracellular ATP and its P2 receptors in innate and adaptive immunity. It promotes inflammation as a danger signal in various chronic inflammatory diseases. Thus, we hypothesize contribution of extracellular ATP and its receptor P2Y 2 in vascular inflammation and atherosclerosis. Approach and Results - Extracellular ATP induced leukocyte rolling, adhesion, and migration in vivo as assessed by intravital microscopy and in sterile peritonitis. To test the role of extracellular ATP in atherosclerosis, ATP or saline as control was injected intraperitoneally 3× a week in low-density lipoprotein receptor -/- mice consuming high cholesterol diet. Atherosclerosis significantly increased after 16 weeks in ATP-treated mice (n=13; control group, 0.26 mm2; ATP group, 0.33 mm2; P=0.01). To gain into the role of ATP-receptor P2Y 2 in ATP-induced leukocyte recruitment, ATP was administered systemically in P2Y 2 -deficient or P2Y 2 -competent mice. In P2Y 2 -deficient mice, the ATP-induced leukocyte adhesion was significantly reduced as assessed by intravital microscopy. P2Y 2 expression in atherosclerosis was measured by real-time polymerase chain reaction and immunohistochemistry and demonstrates an increased expression mainly caused by influx of P2Y 2 -expressing macrophages. To investigate the functional role of P2Y 2 in atherogenesis, P2Y 2 -deficient low-density lipoprotein receptor -/- mice consumed high cholesterol diet. After 16 weeks, P2Y 2 -deficient mice showed significantly reduced atherosclerotic lesions with decreased macrophages compared with P2Y 2 -competent mice (n=11; aortic arch: control group, 0.25 mm 2; P2Y 2 -deficient, 0.14 mm2; P=0.04). Mechanistically, atherosclerotic lesions from P2Y 2 -deficient mice expressed less vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 RNA. Conclusions - We show that extracellular ATP induces vascular inflammation and atherosclerosis via activation of P2Y 2.
publishDate	2016
dc.date.none.fl_str_mv	2016-08
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/11336/151541 Stachon, Peter; Geis, Serjosha; Peikert, Alexander; Heidenreich, Adrian; Anto Michel, Nathaly; et al.; Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor y 2 in Mice; Lippincott Williams; Arteriosclerosis, Thrombosis, and Vascular Biology; 36; 8; 8-2016; 1577-1586 1079-5642 CONICET Digital CONICET
url	http://hdl.handle.net/11336/151541
identifier_str_mv	Stachon, Peter; Geis, Serjosha; Peikert, Alexander; Heidenreich, Adrian; Anto Michel, Nathaly; et al.; Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor y 2 in Mice; Lippincott Williams; Arteriosclerosis, Thrombosis, and Vascular Biology; 36; 8; 8-2016; 1577-1586 1079-5642 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/ATVBAHA.115.307397
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)
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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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Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor y 2 in Mice

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