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MicroRNAs hsa-miR-618 and hsa-miR-297 Might Modulate the Pleiotropic Effects Exerted by Statins in Endothelial Cells Through the Inhibition of ROCK2 Kinase: in-silico Approach

Several studies show that statin therapy improves endothelial function by cholesterol-independent mechanisms called “pleiotropic effects.” These are due to the inhibition of the RhoA/ROCK kinase pathway, its inhibition being an attractive atheroprotective treatment. In addition, recent work has show...

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Autores principales: Leal, Karla, Saavedra, Kathleen, Rebolledo, Camilo, Salazar, Luis A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415262/
https://www.ncbi.nlm.nih.gov/pubmed/34485404
http://dx.doi.org/10.3389/fcvm.2021.704175
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author Leal, Karla
Saavedra, Kathleen
Rebolledo, Camilo
Salazar, Luis A.
author_facet Leal, Karla
Saavedra, Kathleen
Rebolledo, Camilo
Salazar, Luis A.
author_sort Leal, Karla
collection PubMed
description Several studies show that statin therapy improves endothelial function by cholesterol-independent mechanisms called “pleiotropic effects.” These are due to the inhibition of the RhoA/ROCK kinase pathway, its inhibition being an attractive atheroprotective treatment. In addition, recent work has shown that microRNAs, posttranscriptional regulators of gene expression, can affect the response of statins and their efficacy. For this reason, the objective of this study was to identify by bioinformatic analysis possible new microRNAs that could modulate the pleiotropic effects exerted by statins through the inhibition of ROCK kinases. A bioinformatic study was performed in which the differential expression of miRNAs in endothelial cells was compared under two conditions: Control and treated with simvastatin at 10 μM for 24 h, using a microarray. Seven miRNAs were differentially expressed, three up and four down. Within the up group, the miRNAs hsa-miR-618 and hsa-miR-297 present as a predicted target to ROCK2 kinase. Also, functional and enriched pathway analysis showed an association with mechanisms associated with atheroprotective effects. This work shows an in-silico approach of how posttranscriptional regulation mediated by miRNAs could modulate the pleiotropic effects exerted by statins on endothelial cells, through the inhibition of ROCK2 kinase and its effects.
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spelling pubmed-84152622021-09-04 MicroRNAs hsa-miR-618 and hsa-miR-297 Might Modulate the Pleiotropic Effects Exerted by Statins in Endothelial Cells Through the Inhibition of ROCK2 Kinase: in-silico Approach Leal, Karla Saavedra, Kathleen Rebolledo, Camilo Salazar, Luis A. Front Cardiovasc Med Cardiovascular Medicine Several studies show that statin therapy improves endothelial function by cholesterol-independent mechanisms called “pleiotropic effects.” These are due to the inhibition of the RhoA/ROCK kinase pathway, its inhibition being an attractive atheroprotective treatment. In addition, recent work has shown that microRNAs, posttranscriptional regulators of gene expression, can affect the response of statins and their efficacy. For this reason, the objective of this study was to identify by bioinformatic analysis possible new microRNAs that could modulate the pleiotropic effects exerted by statins through the inhibition of ROCK kinases. A bioinformatic study was performed in which the differential expression of miRNAs in endothelial cells was compared under two conditions: Control and treated with simvastatin at 10 μM for 24 h, using a microarray. Seven miRNAs were differentially expressed, three up and four down. Within the up group, the miRNAs hsa-miR-618 and hsa-miR-297 present as a predicted target to ROCK2 kinase. Also, functional and enriched pathway analysis showed an association with mechanisms associated with atheroprotective effects. This work shows an in-silico approach of how posttranscriptional regulation mediated by miRNAs could modulate the pleiotropic effects exerted by statins on endothelial cells, through the inhibition of ROCK2 kinase and its effects. Frontiers Media S.A. 2021-08-16 /pmc/articles/PMC8415262/ /pubmed/34485404 http://dx.doi.org/10.3389/fcvm.2021.704175 Text en Copyright © 2021 Leal, Saavedra, Rebolledo and Salazar. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Leal, Karla
Saavedra, Kathleen
Rebolledo, Camilo
Salazar, Luis A.
MicroRNAs hsa-miR-618 and hsa-miR-297 Might Modulate the Pleiotropic Effects Exerted by Statins in Endothelial Cells Through the Inhibition of ROCK2 Kinase: in-silico Approach
title MicroRNAs hsa-miR-618 and hsa-miR-297 Might Modulate the Pleiotropic Effects Exerted by Statins in Endothelial Cells Through the Inhibition of ROCK2 Kinase: in-silico Approach
title_full MicroRNAs hsa-miR-618 and hsa-miR-297 Might Modulate the Pleiotropic Effects Exerted by Statins in Endothelial Cells Through the Inhibition of ROCK2 Kinase: in-silico Approach
title_fullStr MicroRNAs hsa-miR-618 and hsa-miR-297 Might Modulate the Pleiotropic Effects Exerted by Statins in Endothelial Cells Through the Inhibition of ROCK2 Kinase: in-silico Approach
title_full_unstemmed MicroRNAs hsa-miR-618 and hsa-miR-297 Might Modulate the Pleiotropic Effects Exerted by Statins in Endothelial Cells Through the Inhibition of ROCK2 Kinase: in-silico Approach
title_short MicroRNAs hsa-miR-618 and hsa-miR-297 Might Modulate the Pleiotropic Effects Exerted by Statins in Endothelial Cells Through the Inhibition of ROCK2 Kinase: in-silico Approach
title_sort micrornas hsa-mir-618 and hsa-mir-297 might modulate the pleiotropic effects exerted by statins in endothelial cells through the inhibition of rock2 kinase: in-silico approach
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415262/
https://www.ncbi.nlm.nih.gov/pubmed/34485404
http://dx.doi.org/10.3389/fcvm.2021.704175
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