Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3

Autores
Dube, Prabhatchandra R.; Chikkamenahalli, Lakshmikanth L.; Birnbaumer, Lutz; Vazquez, Guillermo
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background and aims: Recent in vitro studies have showed that in macrophages, deletion of the non-selective Ca2+-permeable channel TRPC3 impairs expression of the osteogenic protein BMP-2. The pathophysiological relevance of this effect in atherosclerotic plaque calcification remains to be determined. Methods: We used Ldlr−/− mice with macrophage-specific loss of TRPC3 (MacTrpc3−/−/Ldlr−/−) to examine the effect of macrophage Trpc3 on plaque calcification and osteogenic features in advanced atherosclerosis. Results: After 25 weeks on high fat diet, aortic root plaques in MacTrpc3−/−/Ldlr−/− mice showed reduced size, lipid and macrophage content compared to controls. Plaque calcification was decreased in MacTrpc3−/−/Ldlr−/− mice, and this was accompanied by marked reduction in BMP-2, Runx-2 and phospho-SMAD1/5 contents within macrophage-rich areas. Expression of Bmp-2 and Runx-2 was also reduced in bone marrow-derived macrophages from MacTrpc3−/−/Ldlr−/− mice. Conclusions: These findings show that, in advanced atherosclerosis, selective deletion of TRPC3 in macrophages favors plaque regression and impairs the activity of a novel macrophage-associated, BMP-2-dependent mechanism of calcification.
Fil: Dube, Prabhatchandra R.. University of Toledo. College of Medicine and Life Sciences; Estados Unidos
Fil: Chikkamenahalli, Lakshmikanth L.. University of Toledo. College of Medicine and Life Sciences; Estados Unidos
Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Vazquez, Guillermo. University of Toledo. College of Medicine and Life Sciences; Estados Unidos
Materia
MACROPHAGE
TRPC3
VASCULAR CALCIFICATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/98877
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/98877
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3Dube, Prabhatchandra R.Chikkamenahalli, Lakshmikanth L.Birnbaumer, LutzVazquez, GuillermoMACROPHAGETRPC3VASCULAR CALCIFICATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background and aims: Recent in vitro studies have showed that in macrophages, deletion of the non-selective Ca2+-permeable channel TRPC3 impairs expression of the osteogenic protein BMP-2. The pathophysiological relevance of this effect in atherosclerotic plaque calcification remains to be determined. Methods: We used Ldlr−/− mice with macrophage-specific loss of TRPC3 (MacTrpc3−/−/Ldlr−/−) to examine the effect of macrophage Trpc3 on plaque calcification and osteogenic features in advanced atherosclerosis. Results: After 25 weeks on high fat diet, aortic root plaques in MacTrpc3−/−/Ldlr−/− mice showed reduced size, lipid and macrophage content compared to controls. Plaque calcification was decreased in MacTrpc3−/−/Ldlr−/− mice, and this was accompanied by marked reduction in BMP-2, Runx-2 and phospho-SMAD1/5 contents within macrophage-rich areas. Expression of Bmp-2 and Runx-2 was also reduced in bone marrow-derived macrophages from MacTrpc3−/−/Ldlr−/− mice. Conclusions: These findings show that, in advanced atherosclerosis, selective deletion of TRPC3 in macrophages favors plaque regression and impairs the activity of a novel macrophage-associated, BMP-2-dependent mechanism of calcification.Fil: Dube, Prabhatchandra R.. University of Toledo. College of Medicine and Life Sciences; Estados UnidosFil: Chikkamenahalli, Lakshmikanth L.. University of Toledo. College of Medicine and Life Sciences; Estados UnidosFil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Vazquez, Guillermo. University of Toledo. College of Medicine and Life Sciences; Estados UnidosElsevier Ireland2018-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/98877Dube, Prabhatchandra R.; Chikkamenahalli, Lakshmikanth L.; Birnbaumer, Lutz; Vazquez, Guillermo; Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3; Elsevier Ireland; Atherosclerosis; 270; 3-2018; 199-2040021-9150CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0021915017314442info:eu-repo/semantics/altIdentifier/doi/10.1016/j.atherosclerosis.2017.12.025info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:30:34Zoai:ri.conicet.gov.ar:11336/98877instacron: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:34982025-10-15 15:30:34.834CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3
title Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3
spellingShingle Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3
Dube, Prabhatchandra R.
MACROPHAGE
TRPC3
VASCULAR CALCIFICATION
title_short Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3
title_full Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3
title_fullStr Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3
title_full_unstemmed Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3
title_sort Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3
dc.creator.none.fl_str_mv Dube, Prabhatchandra R.
Chikkamenahalli, Lakshmikanth L.
Birnbaumer, Lutz
Vazquez, Guillermo
author Dube, Prabhatchandra R.
author_facet Dube, Prabhatchandra R.
Chikkamenahalli, Lakshmikanth L.
Birnbaumer, Lutz
Vazquez, Guillermo
author_role author
author2 Chikkamenahalli, Lakshmikanth L.
Birnbaumer, Lutz
Vazquez, Guillermo
author2_role author
author
author
dc.subject.none.fl_str_mv MACROPHAGE
TRPC3
VASCULAR CALCIFICATION
topic MACROPHAGE
TRPC3
VASCULAR CALCIFICATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background and aims: Recent in vitro studies have showed that in macrophages, deletion of the non-selective Ca2+-permeable channel TRPC3 impairs expression of the osteogenic protein BMP-2. The pathophysiological relevance of this effect in atherosclerotic plaque calcification remains to be determined. Methods: We used Ldlr−/− mice with macrophage-specific loss of TRPC3 (MacTrpc3−/−/Ldlr−/−) to examine the effect of macrophage Trpc3 on plaque calcification and osteogenic features in advanced atherosclerosis. Results: After 25 weeks on high fat diet, aortic root plaques in MacTrpc3−/−/Ldlr−/− mice showed reduced size, lipid and macrophage content compared to controls. Plaque calcification was decreased in MacTrpc3−/−/Ldlr−/− mice, and this was accompanied by marked reduction in BMP-2, Runx-2 and phospho-SMAD1/5 contents within macrophage-rich areas. Expression of Bmp-2 and Runx-2 was also reduced in bone marrow-derived macrophages from MacTrpc3−/−/Ldlr−/− mice. Conclusions: These findings show that, in advanced atherosclerosis, selective deletion of TRPC3 in macrophages favors plaque regression and impairs the activity of a novel macrophage-associated, BMP-2-dependent mechanism of calcification.
Fil: Dube, Prabhatchandra R.. University of Toledo. College of Medicine and Life Sciences; Estados Unidos
Fil: Chikkamenahalli, Lakshmikanth L.. University of Toledo. College of Medicine and Life Sciences; Estados Unidos
Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Vazquez, Guillermo. University of Toledo. College of Medicine and Life Sciences; Estados Unidos
description Background and aims: Recent in vitro studies have showed that in macrophages, deletion of the non-selective Ca2+-permeable channel TRPC3 impairs expression of the osteogenic protein BMP-2. The pathophysiological relevance of this effect in atherosclerotic plaque calcification remains to be determined. Methods: We used Ldlr−/− mice with macrophage-specific loss of TRPC3 (MacTrpc3−/−/Ldlr−/−) to examine the effect of macrophage Trpc3 on plaque calcification and osteogenic features in advanced atherosclerosis. Results: After 25 weeks on high fat diet, aortic root plaques in MacTrpc3−/−/Ldlr−/− mice showed reduced size, lipid and macrophage content compared to controls. Plaque calcification was decreased in MacTrpc3−/−/Ldlr−/− mice, and this was accompanied by marked reduction in BMP-2, Runx-2 and phospho-SMAD1/5 contents within macrophage-rich areas. Expression of Bmp-2 and Runx-2 was also reduced in bone marrow-derived macrophages from MacTrpc3−/−/Ldlr−/− mice. Conclusions: These findings show that, in advanced atherosclerosis, selective deletion of TRPC3 in macrophages favors plaque regression and impairs the activity of a novel macrophage-associated, BMP-2-dependent mechanism of calcification.
publishDate 2018
dc.date.none.fl_str_mv 2018-03
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/11336/98877
Dube, Prabhatchandra R.; Chikkamenahalli, Lakshmikanth L.; Birnbaumer, Lutz; Vazquez, Guillermo; Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3; Elsevier Ireland; Atherosclerosis; 270; 3-2018; 199-204
0021-9150
CONICET Digital
CONICET
url http://hdl.handle.net/11336/98877
identifier_str_mv Dube, Prabhatchandra R.; Chikkamenahalli, Lakshmikanth L.; Birnbaumer, Lutz; Vazquez, Guillermo; Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3; Elsevier Ireland; Atherosclerosis; 270; 3-2018; 199-204
0021-9150
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0021915017314442
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.atherosclerosis.2017.12.025
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
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
_version_ 1846083443583090688
score 13.22299

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