Pioglitazone Induces Cardiomyocyte Apoptosis and Inhibits Cardiomyocyte Hypertrophy Via VEGFR-2 Signaling Pathway

Detalhes bibliográficos
Autor(a) principal: Zhong,Wenliang
Data de Publicação: 2018
Outros Autores: Jin,Wen, Xu,Shanghua, Wu,Yanqing, Luo,Shunxiang, Liang,Minlie, Chen,Lianglong
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Arquivos Brasileiros de Cardiologia (Online)
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2018001400162
Resumo: Abstract Background: Pioglitazone has been widely used as an insulin-sensitizing agent for improving glycemic control in patients with type 2 diabetes mellitus. However, cardiovascular risk and protective effects of pioglitazone remain controversial. Objectives: In this study, we investigated whether pioglitazone affects cardiomyocyte apoptosis and hypertrophy by regulating the VEGFR-2 signaling pathway. Methods: Cardiomyocytes were enzymatically isolated from 1- to 3-day-old Sprague-Dawley rat ventricles. Effects of pioglitazone and the VEGFR-2-selective inhibitor apatinib on cardiomyocyte apoptotic rate was determined using flow cytometry, and hypertrophy was evaluated using [3H]-leucine incorporation. The protein expressions of unphosphorylated and phosphorylated VEGFR-2, Akt, P53, and mTOR were determined by Western-Blotting. Analysis of variance (ANOVA) was used to assess the differences between groups. Results: Pioglitazone and VEGFR-2-selective inhibitor apatinib reduced rat cardiomyocyte viability and cardiomyocyte hypertrophy induced by angiotensin II in vitro. Furthermore, in the same in vitro model, pioglitazone and apatinib significantly increased the expression of Bax and phosphorylated P53 and decreased the expression of phosphorylated VEGFR-2, Akt, and mTOR, which promote cardiomyocyte hypertrophy. Conclusions: These findings indicate that pioglitazone induces cardiomyocyte apoptosis and inhibits cardiomyocyte hypertrophy by modulating the VEGFR-2 signaling pathway.
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spelling Pioglitazone Induces Cardiomyocyte Apoptosis and Inhibits Cardiomyocyte Hypertrophy Via VEGFR-2 Signaling PathwayApoptosisMyocytes, CardiacCardiomegalyHeart Failure/physiopathologyAntihypertensive AgentsThiazolidinedionesInsulin ResistanceAbstract Background: Pioglitazone has been widely used as an insulin-sensitizing agent for improving glycemic control in patients with type 2 diabetes mellitus. However, cardiovascular risk and protective effects of pioglitazone remain controversial. Objectives: In this study, we investigated whether pioglitazone affects cardiomyocyte apoptosis and hypertrophy by regulating the VEGFR-2 signaling pathway. Methods: Cardiomyocytes were enzymatically isolated from 1- to 3-day-old Sprague-Dawley rat ventricles. Effects of pioglitazone and the VEGFR-2-selective inhibitor apatinib on cardiomyocyte apoptotic rate was determined using flow cytometry, and hypertrophy was evaluated using [3H]-leucine incorporation. The protein expressions of unphosphorylated and phosphorylated VEGFR-2, Akt, P53, and mTOR were determined by Western-Blotting. Analysis of variance (ANOVA) was used to assess the differences between groups. Results: Pioglitazone and VEGFR-2-selective inhibitor apatinib reduced rat cardiomyocyte viability and cardiomyocyte hypertrophy induced by angiotensin II in vitro. Furthermore, in the same in vitro model, pioglitazone and apatinib significantly increased the expression of Bax and phosphorylated P53 and decreased the expression of phosphorylated VEGFR-2, Akt, and mTOR, which promote cardiomyocyte hypertrophy. Conclusions: These findings indicate that pioglitazone induces cardiomyocyte apoptosis and inhibits cardiomyocyte hypertrophy by modulating the VEGFR-2 signaling pathway.Sociedade Brasileira de Cardiologia - SBC2018-08-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2018001400162Arquivos Brasileiros de Cardiologia v.111 n.2 2018reponame:Arquivos Brasileiros de Cardiologia (Online)instname:Sociedade Brasileira de Cardiologia (SBC)instacron:SBC10.5935/abc.20180108info:eu-repo/semantics/openAccessZhong,WenliangJin,WenXu,ShanghuaWu,YanqingLuo,ShunxiangLiang,MinlieChen,Lianglongeng2019-01-17T00:00:00Zoai:scielo:S0066-782X2018001400162Revistahttp://www.arquivosonline.com.br/https://old.scielo.br/oai/scielo-oai.php||arquivos@cardiol.br1678-41700066-782Xopendoar:2019-01-17T00:00Arquivos Brasileiros de Cardiologia (Online) - Sociedade Brasileira de Cardiologia (SBC)false
dc.title.none.fl_str_mv Pioglitazone Induces Cardiomyocyte Apoptosis and Inhibits Cardiomyocyte Hypertrophy Via VEGFR-2 Signaling Pathway
title Pioglitazone Induces Cardiomyocyte Apoptosis and Inhibits Cardiomyocyte Hypertrophy Via VEGFR-2 Signaling Pathway
spellingShingle Pioglitazone Induces Cardiomyocyte Apoptosis and Inhibits Cardiomyocyte Hypertrophy Via VEGFR-2 Signaling Pathway
Zhong,Wenliang
Apoptosis
Myocytes, Cardiac
Cardiomegaly
Heart Failure/physiopathology
Antihypertensive Agents
Thiazolidinediones
Insulin Resistance
title_short Pioglitazone Induces Cardiomyocyte Apoptosis and Inhibits Cardiomyocyte Hypertrophy Via VEGFR-2 Signaling Pathway
title_full Pioglitazone Induces Cardiomyocyte Apoptosis and Inhibits Cardiomyocyte Hypertrophy Via VEGFR-2 Signaling Pathway
title_fullStr Pioglitazone Induces Cardiomyocyte Apoptosis and Inhibits Cardiomyocyte Hypertrophy Via VEGFR-2 Signaling Pathway
title_full_unstemmed Pioglitazone Induces Cardiomyocyte Apoptosis and Inhibits Cardiomyocyte Hypertrophy Via VEGFR-2 Signaling Pathway
title_sort Pioglitazone Induces Cardiomyocyte Apoptosis and Inhibits Cardiomyocyte Hypertrophy Via VEGFR-2 Signaling Pathway
author Zhong,Wenliang
author_facet Zhong,Wenliang
Jin,Wen
Xu,Shanghua
Wu,Yanqing
Luo,Shunxiang
Liang,Minlie
Chen,Lianglong
author_role author
author2 Jin,Wen
Xu,Shanghua
Wu,Yanqing
Luo,Shunxiang
Liang,Minlie
Chen,Lianglong
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Zhong,Wenliang
Jin,Wen
Xu,Shanghua
Wu,Yanqing
Luo,Shunxiang
Liang,Minlie
Chen,Lianglong
dc.subject.por.fl_str_mv Apoptosis
Myocytes, Cardiac
Cardiomegaly
Heart Failure/physiopathology
Antihypertensive Agents
Thiazolidinediones
Insulin Resistance
topic Apoptosis
Myocytes, Cardiac
Cardiomegaly
Heart Failure/physiopathology
Antihypertensive Agents
Thiazolidinediones
Insulin Resistance
description Abstract Background: Pioglitazone has been widely used as an insulin-sensitizing agent for improving glycemic control in patients with type 2 diabetes mellitus. However, cardiovascular risk and protective effects of pioglitazone remain controversial. Objectives: In this study, we investigated whether pioglitazone affects cardiomyocyte apoptosis and hypertrophy by regulating the VEGFR-2 signaling pathway. Methods: Cardiomyocytes were enzymatically isolated from 1- to 3-day-old Sprague-Dawley rat ventricles. Effects of pioglitazone and the VEGFR-2-selective inhibitor apatinib on cardiomyocyte apoptotic rate was determined using flow cytometry, and hypertrophy was evaluated using [3H]-leucine incorporation. The protein expressions of unphosphorylated and phosphorylated VEGFR-2, Akt, P53, and mTOR were determined by Western-Blotting. Analysis of variance (ANOVA) was used to assess the differences between groups. Results: Pioglitazone and VEGFR-2-selective inhibitor apatinib reduced rat cardiomyocyte viability and cardiomyocyte hypertrophy induced by angiotensin II in vitro. Furthermore, in the same in vitro model, pioglitazone and apatinib significantly increased the expression of Bax and phosphorylated P53 and decreased the expression of phosphorylated VEGFR-2, Akt, and mTOR, which promote cardiomyocyte hypertrophy. Conclusions: These findings indicate that pioglitazone induces cardiomyocyte apoptosis and inhibits cardiomyocyte hypertrophy by modulating the VEGFR-2 signaling pathway.
publishDate 2018
dc.date.none.fl_str_mv 2018-08-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2018001400162
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2018001400162
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.5935/abc.20180108
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Sociedade Brasileira de Cardiologia - SBC
publisher.none.fl_str_mv Sociedade Brasileira de Cardiologia - SBC
dc.source.none.fl_str_mv Arquivos Brasileiros de Cardiologia v.111 n.2 2018
reponame:Arquivos Brasileiros de Cardiologia (Online)
instname:Sociedade Brasileira de Cardiologia (SBC)
instacron:SBC
instname_str Sociedade Brasileira de Cardiologia (SBC)
instacron_str SBC
institution SBC
reponame_str Arquivos Brasileiros de Cardiologia (Online)
collection Arquivos Brasileiros de Cardiologia (Online)
repository.name.fl_str_mv Arquivos Brasileiros de Cardiologia (Online) - Sociedade Brasileira de Cardiologia (SBC)
repository.mail.fl_str_mv ||arquivos@cardiol.br
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