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Suppression of Induced microRNA-15b Prevents Rapid Loss of Cardiac Function in a Dicer Depleted Model of Cardiac Dysfunction

BACKGROUND: Dicer endonuclease, critical for maturation of miRNAs, is depleted in certain forms of cardiomyopathy which results in differential expression of certain microRNAs. We sought to elucidate the mechanisms underlying the rapid loss of cardiac function following cardiac-specific Dicer deplet...

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Autores principales: Roy, Sashwati, Banerjee, Jaideep, Gnyawali, Surya C., Khanna, Savita, He, Guanglong, Pfeiffer, Douglas, Zweier, Jay L., Sen, Chandan K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3686742/
https://www.ncbi.nlm.nih.gov/pubmed/23840532
http://dx.doi.org/10.1371/journal.pone.0066789
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author Roy, Sashwati
Banerjee, Jaideep
Gnyawali, Surya C.
Khanna, Savita
He, Guanglong
Pfeiffer, Douglas
Zweier, Jay L.
Sen, Chandan K.
author_facet Roy, Sashwati
Banerjee, Jaideep
Gnyawali, Surya C.
Khanna, Savita
He, Guanglong
Pfeiffer, Douglas
Zweier, Jay L.
Sen, Chandan K.
author_sort Roy, Sashwati
collection PubMed
description BACKGROUND: Dicer endonuclease, critical for maturation of miRNAs, is depleted in certain forms of cardiomyopathy which results in differential expression of certain microRNAs. We sought to elucidate the mechanisms underlying the rapid loss of cardiac function following cardiac-specific Dicer depletion in adult mice. RESULTS: Conditional Dicer deletion in the adult murine myocardium demonstrated compromised heart function, mitochondrial dysfunction and oxidant stress. Elevated miR-15b was observed as an early response to Dicer depletion and was found to silence Pim-1 kinase, a protein responsible for maintaining mitochondrial integrity and function. Anti-miRNA based suppression of induced miRNA-15b rescued the function of Dicer-depleted adult heart and attenuated hypertrophy. CONCLUSIONS: Anti-miRNA based suppression of inducible miRNA-15b can prevent rapid loss of cardiac function in a Dicer-depleted adult heart and can be a key approach worthy of therapeutic consideration.
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spelling pubmed-36867422013-07-09 Suppression of Induced microRNA-15b Prevents Rapid Loss of Cardiac Function in a Dicer Depleted Model of Cardiac Dysfunction Roy, Sashwati Banerjee, Jaideep Gnyawali, Surya C. Khanna, Savita He, Guanglong Pfeiffer, Douglas Zweier, Jay L. Sen, Chandan K. PLoS One Research Article BACKGROUND: Dicer endonuclease, critical for maturation of miRNAs, is depleted in certain forms of cardiomyopathy which results in differential expression of certain microRNAs. We sought to elucidate the mechanisms underlying the rapid loss of cardiac function following cardiac-specific Dicer depletion in adult mice. RESULTS: Conditional Dicer deletion in the adult murine myocardium demonstrated compromised heart function, mitochondrial dysfunction and oxidant stress. Elevated miR-15b was observed as an early response to Dicer depletion and was found to silence Pim-1 kinase, a protein responsible for maintaining mitochondrial integrity and function. Anti-miRNA based suppression of induced miRNA-15b rescued the function of Dicer-depleted adult heart and attenuated hypertrophy. CONCLUSIONS: Anti-miRNA based suppression of inducible miRNA-15b can prevent rapid loss of cardiac function in a Dicer-depleted adult heart and can be a key approach worthy of therapeutic consideration. Public Library of Science 2013-06-19 /pmc/articles/PMC3686742/ /pubmed/23840532 http://dx.doi.org/10.1371/journal.pone.0066789 Text en © 2013 Roy et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Roy, Sashwati
Banerjee, Jaideep
Gnyawali, Surya C.
Khanna, Savita
He, Guanglong
Pfeiffer, Douglas
Zweier, Jay L.
Sen, Chandan K.
Suppression of Induced microRNA-15b Prevents Rapid Loss of Cardiac Function in a Dicer Depleted Model of Cardiac Dysfunction
title Suppression of Induced microRNA-15b Prevents Rapid Loss of Cardiac Function in a Dicer Depleted Model of Cardiac Dysfunction
title_full Suppression of Induced microRNA-15b Prevents Rapid Loss of Cardiac Function in a Dicer Depleted Model of Cardiac Dysfunction
title_fullStr Suppression of Induced microRNA-15b Prevents Rapid Loss of Cardiac Function in a Dicer Depleted Model of Cardiac Dysfunction
title_full_unstemmed Suppression of Induced microRNA-15b Prevents Rapid Loss of Cardiac Function in a Dicer Depleted Model of Cardiac Dysfunction
title_short Suppression of Induced microRNA-15b Prevents Rapid Loss of Cardiac Function in a Dicer Depleted Model of Cardiac Dysfunction
title_sort suppression of induced microrna-15b prevents rapid loss of cardiac function in a dicer depleted model of cardiac dysfunction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3686742/
https://www.ncbi.nlm.nih.gov/pubmed/23840532
http://dx.doi.org/10.1371/journal.pone.0066789
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