Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells
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, includ...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Sociedade Brasileira de Cardiologia (SBC)
2015-03-01
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| Series: | Arquivos Brasileiros de Cardiologia |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2015000300004&lng=en&tlng=en |
| _version_ | 1811210108137373696 |
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| author | Alvaro Cerda Cristina Moreno Fajardo Rodrigo Gouveia Basso Mario Hiroyuki Hirata Rosario Dominguez Crespo Hirata |
| author_facet | Alvaro Cerda Cristina Moreno Fajardo Rodrigo Gouveia Basso Mario Hiroyuki Hirata Rosario Dominguez Crespo Hirata |
| author_sort | Alvaro Cerda |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T04:49:27Z |
| format | Article |
| id | doaj.art-d6632e4558154528a93a1d742676cef0 |
| institution | Directory Open Access Journal |
| issn | 1678-4170 |
| language | English |
| last_indexed | 2024-04-12T04:49:27Z |
| publishDate | 2015-03-01 |
| publisher | Sociedade Brasileira de Cardiologia (SBC) |
| record_format | Article |
| series | Arquivos Brasileiros de Cardiologia |
| spelling | doaj.art-d6632e4558154528a93a1d742676cef02022-12-22T03:47:21ZengSociedade Brasileira de Cardiologia (SBC)Arquivos Brasileiros de Cardiologia1678-41702015-03-01104319520110.5935/abc.20140192S0066-782X2015000300004Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial CellsAlvaro CerdaCristina Moreno FajardoRodrigo Gouveia BassoMario Hiroyuki HirataRosario Dominguez Crespo HirataBackground: 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2015000300004&lng=en&tlng=enÓxido NítricoColesterolInibidores de Hidroximetilglutaril-CoA RedutasesCélulas EndoteliaismicroRNAs |
| spellingShingle | Alvaro Cerda Cristina Moreno Fajardo Rodrigo Gouveia Basso Mario Hiroyuki Hirata Rosario Dominguez Crespo Hirata Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells Arquivos Brasileiros de Cardiologia Óxido Nítrico Colesterol Inibidores de Hidroximetilglutaril-CoA Redutases Células Endoteliais microRNAs |
| title | 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_short | 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 |
| topic | Óxido Nítrico Colesterol Inibidores de Hidroximetilglutaril-CoA Redutases Células Endoteliais microRNAs |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2015000300004&lng=en&tlng=en |
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