Cargando…

MiR-30-Regulated Autophagy Mediates Angiotensin II-Induced Myocardial Hypertrophy

Dysregulated autophagy may lead to the development of disease. Role of autophagy and the diagnostic potential of microRNAs that regulate the autophagy in cardiac hypertrophy have not been evaluated. A rat model of cardiac hypertrophy was established using transverse abdominal aortic constriction (op...

Descripción completa

Detalles Bibliográficos
Autores principales: Pan, Wei, Zhong, Yun, Cheng, Chuanfang, Liu, Benrong, Wang, Li, Li, Aiqun, Xiong, Longgen, Liu, Shiming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541228/
https://www.ncbi.nlm.nih.gov/pubmed/23326547
http://dx.doi.org/10.1371/journal.pone.0053950
_version_ 1782255324706635776
author Pan, Wei
Zhong, Yun
Cheng, Chuanfang
Liu, Benrong
Wang, Li
Li, Aiqun
Xiong, Longgen
Liu, Shiming
author_facet Pan, Wei
Zhong, Yun
Cheng, Chuanfang
Liu, Benrong
Wang, Li
Li, Aiqun
Xiong, Longgen
Liu, Shiming
author_sort Pan, Wei
collection PubMed
description Dysregulated autophagy may lead to the development of disease. Role of autophagy and the diagnostic potential of microRNAs that regulate the autophagy in cardiac hypertrophy have not been evaluated. A rat model of cardiac hypertrophy was established using transverse abdominal aortic constriction (operation group). Cardiomyocyte autophagy was enhanced in rats from the operation group, compared with those in the sham operation group. Moreover, the operation group showed up-regulation of beclin-1 (an autophagy-related gene), and down-regulation of miR-30 in cardiac tissue. The effects of inhibition and over-expression of the beclin-1 gene on the expression of hypertrophy-related genes and on autophagy were assessed. Angiotensin II-induced myocardial hypertrophy was found to be mediated by over-expression of the beclin-1 gene. A dual luciferase reporter assay confirmed that beclin-1 was a target gene of miR-30a. miR-30a induced alterations in beclin-1 gene expression and autophagy in cardiomyocytes. Treatment of cardiomyocytes with miR-30a mimic attenuated the Angiotensin II-induced up-regulation of hypertrophy-related genes and decreased in the cardiomyocyte surface area. Conversely, treatment with miR-30a inhibitor enhanced the up-regulation of hypertrophy-related genes and increased the surface area of cardiomyocytes induced by Angiotensin II. In addition, circulating miR-30 was elevated in patients with left ventricular hypertrophy, and circulating miR-30 was positively associated with left ventricular wall thickness. Collectively, these above-mentioned results suggest that Angiotensin II induces down-regulation of miR-30 in cardiomyocytes, which in turn promotes myocardial hypertrophy through excessive autophagy. Circulating miR-30 may be an important marker for the diagnosis of left ventricular hypertrophy.
format Online
Article
Text
id pubmed-3541228
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-35412282013-01-16 MiR-30-Regulated Autophagy Mediates Angiotensin II-Induced Myocardial Hypertrophy Pan, Wei Zhong, Yun Cheng, Chuanfang Liu, Benrong Wang, Li Li, Aiqun Xiong, Longgen Liu, Shiming PLoS One Research Article Dysregulated autophagy may lead to the development of disease. Role of autophagy and the diagnostic potential of microRNAs that regulate the autophagy in cardiac hypertrophy have not been evaluated. A rat model of cardiac hypertrophy was established using transverse abdominal aortic constriction (operation group). Cardiomyocyte autophagy was enhanced in rats from the operation group, compared with those in the sham operation group. Moreover, the operation group showed up-regulation of beclin-1 (an autophagy-related gene), and down-regulation of miR-30 in cardiac tissue. The effects of inhibition and over-expression of the beclin-1 gene on the expression of hypertrophy-related genes and on autophagy were assessed. Angiotensin II-induced myocardial hypertrophy was found to be mediated by over-expression of the beclin-1 gene. A dual luciferase reporter assay confirmed that beclin-1 was a target gene of miR-30a. miR-30a induced alterations in beclin-1 gene expression and autophagy in cardiomyocytes. Treatment of cardiomyocytes with miR-30a mimic attenuated the Angiotensin II-induced up-regulation of hypertrophy-related genes and decreased in the cardiomyocyte surface area. Conversely, treatment with miR-30a inhibitor enhanced the up-regulation of hypertrophy-related genes and increased the surface area of cardiomyocytes induced by Angiotensin II. In addition, circulating miR-30 was elevated in patients with left ventricular hypertrophy, and circulating miR-30 was positively associated with left ventricular wall thickness. Collectively, these above-mentioned results suggest that Angiotensin II induces down-regulation of miR-30 in cardiomyocytes, which in turn promotes myocardial hypertrophy through excessive autophagy. Circulating miR-30 may be an important marker for the diagnosis of left ventricular hypertrophy. Public Library of Science 2013-01-09 /pmc/articles/PMC3541228/ /pubmed/23326547 http://dx.doi.org/10.1371/journal.pone.0053950 Text en © 2013 Pan 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
Pan, Wei
Zhong, Yun
Cheng, Chuanfang
Liu, Benrong
Wang, Li
Li, Aiqun
Xiong, Longgen
Liu, Shiming
MiR-30-Regulated Autophagy Mediates Angiotensin II-Induced Myocardial Hypertrophy
title MiR-30-Regulated Autophagy Mediates Angiotensin II-Induced Myocardial Hypertrophy
title_full MiR-30-Regulated Autophagy Mediates Angiotensin II-Induced Myocardial Hypertrophy
title_fullStr MiR-30-Regulated Autophagy Mediates Angiotensin II-Induced Myocardial Hypertrophy
title_full_unstemmed MiR-30-Regulated Autophagy Mediates Angiotensin II-Induced Myocardial Hypertrophy
title_short MiR-30-Regulated Autophagy Mediates Angiotensin II-Induced Myocardial Hypertrophy
title_sort mir-30-regulated autophagy mediates angiotensin ii-induced myocardial hypertrophy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541228/
https://www.ncbi.nlm.nih.gov/pubmed/23326547
http://dx.doi.org/10.1371/journal.pone.0053950
work_keys_str_mv AT panwei mir30regulatedautophagymediatesangiotensiniiinducedmyocardialhypertrophy
AT zhongyun mir30regulatedautophagymediatesangiotensiniiinducedmyocardialhypertrophy
AT chengchuanfang mir30regulatedautophagymediatesangiotensiniiinducedmyocardialhypertrophy
AT liubenrong mir30regulatedautophagymediatesangiotensiniiinducedmyocardialhypertrophy
AT wangli mir30regulatedautophagymediatesangiotensiniiinducedmyocardialhypertrophy
AT liaiqun mir30regulatedautophagymediatesangiotensiniiinducedmyocardialhypertrophy
AT xionglonggen mir30regulatedautophagymediatesangiotensiniiinducedmyocardialhypertrophy
AT liushiming mir30regulatedautophagymediatesangiotensiniiinducedmyocardialhypertrophy