Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells

Detalhes bibliográficos
Autor(a) principal: Cerda,Alvaro
Data de Publicação: 2015
Outros Autores: Fajardo,Cristina Moreno, Basso,Rodrigo Gouveia, Hirata,Mario Hiroyuki, Hirata,Rosario Dominguez Crespo
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=S0066-782X2015000300004
Resumo: Background: Nitric oxide (NO) has been largely associated with cardiovascular protection through improvement of endothelial function. Recently, new evidence about modulation of NO release by microRNAs (miRs) has been reported, which could be involved with statin-dependent pleiotropic effects, including anti-inflammatory properties related to vascular endothelium function. Objective: To evaluate the effects of cholesterol-lowering drugs including the inhibitors of cholesterol synthesis, atorvastatin and simvastatin, and the inhibitor of cholesterol absorption ezetimibe on NO release, NOS3 mRNA expression and miRs potentially involved in NO bioavailability. Methods: Human umbilical vein endothelial cells (HUVEC) were exposed to atorvastatin, simvastatin or ezetimibe (0 to 5.0 μM). Cells were submitted to total RNA extraction and relative quantification of NOS3 mRNA and miRs -221, -222 and -1303 by qPCR. NO release was measured in supernatants by ozone-chemiluminescence. Results: Both statins increased NO levels and NOS3 mRNA expression but no influence was observed for ezetimibe treatment. Atorvastatin, simvastatin and ezetimibe down-regulated the expression of miR-221, whereas miR-222 was reduced only after the atorvastatin treatment. The magnitude of the reduction of miR-221 and miR-222 after treatment with statins correlated with the increment in NOS3 mRNA levels. No influence was observed on the miR-1303 expression after treatments. Conclusion: NO release in endothelial cells is increased by statins but not by the inhibitor of cholesterol absorption, ezetimibe. Our results provide new evidence about the participation of regulatory miRs 221/222 on NO release induction mediated by statins. Although ezetimibe did not modulate NO levels, the down-regulation of miR-221 could involve potential effects on endothelial function.
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spelling Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial CellsNitric OxideCholesterolHydroxymethylglutaryl-CoA Reductase InhibitorsEndothelial CellsmicroRNAs Background: Nitric oxide (NO) has been largely associated with cardiovascular protection through improvement of endothelial function. Recently, new evidence about modulation of NO release by microRNAs (miRs) has been reported, which could be involved with statin-dependent pleiotropic effects, including anti-inflammatory properties related to vascular endothelium function. Objective: To evaluate the effects of cholesterol-lowering drugs including the inhibitors of cholesterol synthesis, atorvastatin and simvastatin, and the inhibitor of cholesterol absorption ezetimibe on NO release, NOS3 mRNA expression and miRs potentially involved in NO bioavailability. Methods: Human umbilical vein endothelial cells (HUVEC) were exposed to atorvastatin, simvastatin or ezetimibe (0 to 5.0 μM). Cells were submitted to total RNA extraction and relative quantification of NOS3 mRNA and miRs -221, -222 and -1303 by qPCR. NO release was measured in supernatants by ozone-chemiluminescence. Results: Both statins increased NO levels and NOS3 mRNA expression but no influence was observed for ezetimibe treatment. Atorvastatin, simvastatin and ezetimibe down-regulated the expression of miR-221, whereas miR-222 was reduced only after the atorvastatin treatment. The magnitude of the reduction of miR-221 and miR-222 after treatment with statins correlated with the increment in NOS3 mRNA levels. No influence was observed on the miR-1303 expression after treatments. Conclusion: NO release in endothelial cells is increased by statins but not by the inhibitor of cholesterol absorption, ezetimibe. Our results provide new evidence about the participation of regulatory miRs 221/222 on NO release induction mediated by statins. Although ezetimibe did not modulate NO levels, the down-regulation of miR-221 could involve potential effects on endothelial function. Sociedade Brasileira de Cardiologia - SBC2015-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2015000300004Arquivos Brasileiros de Cardiologia v.104 n.3 2015reponame:Arquivos Brasileiros de Cardiologia (Online)instname:Sociedade Brasileira de Cardiologia (SBC)instacron:SBC10.5935/abc.20140192info:eu-repo/semantics/openAccessCerda,AlvaroFajardo,Cristina MorenoBasso,Rodrigo GouveiaHirata,Mario HiroyukiHirata,Rosario Dominguez Crespoeng2015-04-07T00:00:00Zoai:scielo:S0066-782X2015000300004Revistahttp://www.arquivosonline.com.br/https://old.scielo.br/oai/scielo-oai.php||arquivos@cardiol.br1678-41700066-782Xopendoar:2015-04-07T00:00Arquivos Brasileiros de Cardiologia (Online) - Sociedade Brasileira de Cardiologia (SBC)false
dc.title.none.fl_str_mv Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells
title Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells
spellingShingle Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells
Cerda,Alvaro
Nitric Oxide
Cholesterol
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Endothelial Cells
microRNAs
title_short Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells
title_full Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells
title_fullStr Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells
title_full_unstemmed Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells
title_sort Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells
author Cerda,Alvaro
author_facet Cerda,Alvaro
Fajardo,Cristina Moreno
Basso,Rodrigo Gouveia
Hirata,Mario Hiroyuki
Hirata,Rosario Dominguez Crespo
author_role author
author2 Fajardo,Cristina Moreno
Basso,Rodrigo Gouveia
Hirata,Mario Hiroyuki
Hirata,Rosario Dominguez Crespo
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Cerda,Alvaro
Fajardo,Cristina Moreno
Basso,Rodrigo Gouveia
Hirata,Mario Hiroyuki
Hirata,Rosario Dominguez Crespo
dc.subject.por.fl_str_mv Nitric Oxide
Cholesterol
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Endothelial Cells
microRNAs
topic Nitric Oxide
Cholesterol
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Endothelial Cells
microRNAs
description Background: Nitric oxide (NO) has been largely associated with cardiovascular protection through improvement of endothelial function. Recently, new evidence about modulation of NO release by microRNAs (miRs) has been reported, which could be involved with statin-dependent pleiotropic effects, including anti-inflammatory properties related to vascular endothelium function. Objective: To evaluate the effects of cholesterol-lowering drugs including the inhibitors of cholesterol synthesis, atorvastatin and simvastatin, and the inhibitor of cholesterol absorption ezetimibe on NO release, NOS3 mRNA expression and miRs potentially involved in NO bioavailability. Methods: Human umbilical vein endothelial cells (HUVEC) were exposed to atorvastatin, simvastatin or ezetimibe (0 to 5.0 μM). Cells were submitted to total RNA extraction and relative quantification of NOS3 mRNA and miRs -221, -222 and -1303 by qPCR. NO release was measured in supernatants by ozone-chemiluminescence. Results: Both statins increased NO levels and NOS3 mRNA expression but no influence was observed for ezetimibe treatment. Atorvastatin, simvastatin and ezetimibe down-regulated the expression of miR-221, whereas miR-222 was reduced only after the atorvastatin treatment. The magnitude of the reduction of miR-221 and miR-222 after treatment with statins correlated with the increment in NOS3 mRNA levels. No influence was observed on the miR-1303 expression after treatments. Conclusion: NO release in endothelial cells is increased by statins but not by the inhibitor of cholesterol absorption, ezetimibe. Our results provide new evidence about the participation of regulatory miRs 221/222 on NO release induction mediated by statins. Although ezetimibe did not modulate NO levels, the down-regulation of miR-221 could involve potential effects on endothelial function.
publishDate 2015
dc.date.none.fl_str_mv 2015-03-01
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=S0066-782X2015000300004
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2015000300004
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.5935/abc.20140192
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.104 n.3 2015
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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