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

Abstract: 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 b...

Descripción completa

Detalles Bibliográficos
Autores principales: Dube, Prabhatchandra R., Chikkamenahalli, Lakshmikanth L., Birnbaumer, Lutz, Vazquez, Guillermo
Formato: Artículo
Lenguaje:Inglés
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8715
Aporte de:
id I33-R139123456789-8715
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic ARTERIOESCLEROSIS
CALCIFICACION
OSTEOGENESIS
FOSFORILACION
spellingShingle ARTERIOESCLEROSIS
CALCIFICACION
OSTEOGENESIS
FOSFORILACION
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
topic_facet ARTERIOESCLEROSIS
CALCIFICACION
OSTEOGENESIS
FOSFORILACION
description Abstract: 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 macrophageassociated, BMP-2-dependent mechanism of calcification.
format Artículo
author Dube, Prabhatchandra R.
Chikkamenahalli, Lakshmikanth L.
Birnbaumer, Lutz
Vazquez, Guillermo
author_facet Dube, Prabhatchandra R.
Chikkamenahalli, Lakshmikanth L.
Birnbaumer, Lutz
Vazquez, Guillermo
author_sort Dube, Prabhatchandra R.
title Reduced calcification and osteogenic features in advanced atherosclerotic plaques of mice with macrophage-specific loss of TRPC3
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
publisher Elsevier
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8715
work_keys_str_mv AT dubeprabhatchandrar reducedcalcificationandosteogenicfeaturesinadvancedatheroscleroticplaquesofmicewithmacrophagespecificlossoftrpc3
AT chikkamenahallilakshmikanthl reducedcalcificationandosteogenicfeaturesinadvancedatheroscleroticplaquesofmicewithmacrophagespecificlossoftrpc3
AT birnbaumerlutz reducedcalcificationandosteogenicfeaturesinadvancedatheroscleroticplaquesofmicewithmacrophagespecificlossoftrpc3
AT vazquezguillermo reducedcalcificationandosteogenicfeaturesinadvancedatheroscleroticplaquesofmicewithmacrophagespecificlossoftrpc3
bdutipo_str Repositorios
_version_ 1764820528472784899