Reduced necrosis and content of apoptotic M1 macrophages in advanced atherosclerotic plaques of mice with macrophage-specific loss of Trpc3

Reduced necrosis and content of apoptotic M1 macrophages in advanced atherosclerotic plaques of mice with macrophage-specific loss of Trpc3

Abstract: In previous work we reported that ApoeKO mice transplanted with bone marrow cells deficient in the Transient Receptor Potential Canonical 3 (TRPC3) channel have reduced necrosis and number of apoptotic macrophages in advanced atherosclerotic plaques. Also, in vitro studies with polarized macrophages derived from mice with macrophage-specific loss of TRPC3 showed that M1, but not M2 macrophages, deficient in Trpc3 are less susceptible to ER stress-induced apoptosis than Trpc3 expressing cells. The questions remained (a) whether the plaque phenotype in transplanted mice resulted from a genuine effect of Trpc3 on macrophages, and (b) whether the reduced necrosis and macrophage apoptosis in plaques of these mice was a manifestation of the selective effect of TRPC3 on apoptosis of M1 macrophages previously observed in vitro. Here, we addressed these questions using Ldlr knockout (Ldlr-/-) mice with macrophage-specific loss of Trpc3 (MacTrpc3-/-/Ldlr-/- → Ldlr-/-). Compared to controls, we observed decreased plaque necrosis and number of apoptotic macrophages in MacTrpc3-/-/Ldlr-/- → Ldlr-/- mice. Immunohistochemical analysis revealed a reduction in apoptotic M1, but not apoptotic M2 macrophages. These findings confirm an effect of TRPC3 on plaque necrosis and support the notion that this is likely a reflection of the reduced susceptibility of Trpc3-deficient M1 macrophages to apoptosis.

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Main Authors: Solanki, Sumeet, Dube, Prabhatchandra R., Birnbaumer, Lutz, Vazquez, Guillermo
Format: Artículo biblioteca
Language:eng
Published: Nature Research 2017
Subjects:NECROSIS, APOPTOSIS, ARTERIOESCLEROSIS, MARCADORES BIOLOGICOS,
Online Access:https://repositorio.uca.edu.ar/handle/123456789/8732
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spelling oai:ucacris:123456789-87322019-09-13T04:15:32Z Reduced necrosis and content of apoptotic M1 macrophages in advanced atherosclerotic plaques of mice with macrophage-specific loss of Trpc3 Solanki, Sumeet Dube, Prabhatchandra R. Birnbaumer, Lutz Vazquez, Guillermo NECROSIS APOPTOSIS ARTERIOESCLEROSIS MARCADORES BIOLOGICOS Abstract: In previous work we reported that ApoeKO mice transplanted with bone marrow cells deficient in the Transient Receptor Potential Canonical 3 (TRPC3) channel have reduced necrosis and number of apoptotic macrophages in advanced atherosclerotic plaques. Also, in vitro studies with polarized macrophages derived from mice with macrophage-specific loss of TRPC3 showed that M1, but not M2 macrophages, deficient in Trpc3 are less susceptible to ER stress-induced apoptosis than Trpc3 expressing cells. The questions remained (a) whether the plaque phenotype in transplanted mice resulted from a genuine effect of Trpc3 on macrophages, and (b) whether the reduced necrosis and macrophage apoptosis in plaques of these mice was a manifestation of the selective effect of TRPC3 on apoptosis of M1 macrophages previously observed in vitro. Here, we addressed these questions using Ldlr knockout (Ldlr-/-) mice with macrophage-specific loss of Trpc3 (MacTrpc3-/-/Ldlr-/- → Ldlr-/-). Compared to controls, we observed decreased plaque necrosis and number of apoptotic macrophages in MacTrpc3-/-/Ldlr-/- → Ldlr-/- mice. Immunohistochemical analysis revealed a reduction in apoptotic M1, but not apoptotic M2 macrophages. These findings confirm an effect of TRPC3 on plaque necrosis and support the notion that this is likely a reflection of the reduced susceptibility of Trpc3-deficient M1 macrophages to apoptosis. 2019-09-12T19:22:29Z 2019-09-12T19:22:29Z 2017 Artículo Solanki S, Dube PR, Birnbaumer L, Vazquez G. Reduced Necrosis and Content of Apoptotic M1 Macrophages in Advanced Atherosclerotic Plaques of Mice With Macrophage-Specific Loss of Trpc3 [en línea]. Scientific Reports. 2017;7:42526. doi:10.1038/srep42526 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8732 2045-2322 https://repositorio.uca.edu.ar/handle/123456789/8732 10.1038/srep42526 28186192 eng Acceso Abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Research Scientific Reports. 2017;7:42526
institution UCA
collection DSpace
country Argentina
countrycode AR
component Bibliográfico
access En linea
databasecode dig-uca
tag biblioteca
region America del Sur
libraryname Sistema de bibliotecas de la UCA
language eng
topic NECROSIS
APOPTOSIS
ARTERIOESCLEROSIS
MARCADORES BIOLOGICOS
NECROSIS
APOPTOSIS
ARTERIOESCLEROSIS
MARCADORES BIOLOGICOS
spellingShingle NECROSIS
APOPTOSIS
ARTERIOESCLEROSIS
MARCADORES BIOLOGICOS
NECROSIS
APOPTOSIS
ARTERIOESCLEROSIS
MARCADORES BIOLOGICOS
Solanki, Sumeet
Dube, Prabhatchandra R.
Birnbaumer, Lutz
Vazquez, Guillermo
Reduced necrosis and content of apoptotic M1 macrophages in advanced atherosclerotic plaques of mice with macrophage-specific loss of Trpc3
description Abstract: In previous work we reported that ApoeKO mice transplanted with bone marrow cells deficient in the Transient Receptor Potential Canonical 3 (TRPC3) channel have reduced necrosis and number of apoptotic macrophages in advanced atherosclerotic plaques. Also, in vitro studies with polarized macrophages derived from mice with macrophage-specific loss of TRPC3 showed that M1, but not M2 macrophages, deficient in Trpc3 are less susceptible to ER stress-induced apoptosis than Trpc3 expressing cells. The questions remained (a) whether the plaque phenotype in transplanted mice resulted from a genuine effect of Trpc3 on macrophages, and (b) whether the reduced necrosis and macrophage apoptosis in plaques of these mice was a manifestation of the selective effect of TRPC3 on apoptosis of M1 macrophages previously observed in vitro. Here, we addressed these questions using Ldlr knockout (Ldlr-/-) mice with macrophage-specific loss of Trpc3 (MacTrpc3-/-/Ldlr-/- → Ldlr-/-). Compared to controls, we observed decreased plaque necrosis and number of apoptotic macrophages in MacTrpc3-/-/Ldlr-/- → Ldlr-/- mice. Immunohistochemical analysis revealed a reduction in apoptotic M1, but not apoptotic M2 macrophages. These findings confirm an effect of TRPC3 on plaque necrosis and support the notion that this is likely a reflection of the reduced susceptibility of Trpc3-deficient M1 macrophages to apoptosis.
format Artículo
topic_facet NECROSIS
APOPTOSIS
ARTERIOESCLEROSIS
MARCADORES BIOLOGICOS
author Solanki, Sumeet
Dube, Prabhatchandra R.
Birnbaumer, Lutz
Vazquez, Guillermo
author_facet Solanki, Sumeet
Dube, Prabhatchandra R.
Birnbaumer, Lutz
Vazquez, Guillermo
author_sort Solanki, Sumeet
title Reduced necrosis and content of apoptotic M1 macrophages in advanced atherosclerotic plaques of mice with macrophage-specific loss of Trpc3
title_short Reduced necrosis and content of apoptotic M1 macrophages in advanced atherosclerotic plaques of mice with macrophage-specific loss of Trpc3
title_full Reduced necrosis and content of apoptotic M1 macrophages in advanced atherosclerotic plaques of mice with macrophage-specific loss of Trpc3
title_fullStr Reduced necrosis and content of apoptotic M1 macrophages in advanced atherosclerotic plaques of mice with macrophage-specific loss of Trpc3
title_full_unstemmed Reduced necrosis and content of apoptotic M1 macrophages in advanced atherosclerotic plaques of mice with macrophage-specific loss of Trpc3
title_sort reduced necrosis and content of apoptotic m1 macrophages in advanced atherosclerotic plaques of mice with macrophage-specific loss of trpc3
publisher Nature Research
publishDate 2017
url https://repositorio.uca.edu.ar/handle/123456789/8732
work_keys_str_mv AT solankisumeet reducednecrosisandcontentofapoptoticm1macrophagesinadvancedatheroscleroticplaquesofmicewithmacrophagespecificlossoftrpc3
AT dubeprabhatchandrar reducednecrosisandcontentofapoptoticm1macrophagesinadvancedatheroscleroticplaquesofmicewithmacrophagespecificlossoftrpc3
AT birnbaumerlutz reducednecrosisandcontentofapoptoticm1macrophagesinadvancedatheroscleroticplaquesofmicewithmacrophagespecificlossoftrpc3
AT vazquezguillermo reducednecrosisandcontentofapoptoticm1macrophagesinadvancedatheroscleroticplaquesofmicewithmacrophagespecificlossoftrpc3
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