Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice

Sepsis-induced myocardial dysfunction represents a major cause of death in intensive care units. Dysregulated microRNAs (miR)-155 has been implicated in multiple cardiovascular diseases and miR-155 can be induced by lipopolysaccharide (LPS). However, the role of miR-155 in LPS-induced cardiac dysfun...

Full description

Bibliographic Details
Main Authors:	Wang, Hui, Bei, Yihua, Huang, Peipei, Zhou, Qiulian, Shi, Jing, Sun, Qi, Zhong, Jiuchang, Li, Xinli, Kong, Xiangqing, Xiao, Junjie
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095684/

id	pubmed-5095684
recordtype	oai_dc
spelling	pubmed-50956842016-11-18 Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice Wang, Hui Bei, Yihua Huang, Peipei Zhou, Qiulian Shi, Jing Sun, Qi Zhong, Jiuchang Li, Xinli Kong, Xiangqing Xiao, Junjie Original Article Sepsis-induced myocardial dysfunction represents a major cause of death in intensive care units. Dysregulated microRNAs (miR)-155 has been implicated in multiple cardiovascular diseases and miR-155 can be induced by lipopolysaccharide (LPS). However, the role of miR-155 in LPS-induced cardiac dysfunction is unclear. Septic cardiac dysfunction in mice was induced by intraperitoneal injection of LPS (5 mg/kg) and miR-155 was found to be significantly increased in heart challenged with LPS. Pharmacological inhibition of miR-155 using antagomiR improved cardiac function and suppressed cardiac apoptosis induced by LPS in mice as determined by echocardiography, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay, and Western blot for Bax and Bcl-2, while overexpression of miR-155 using agomiR had inverse effects. Pea15a was identified as a target gene of miR-155, mediating its effects in controlling apoptosis of cardiomyocytes as evidenced by luciferase reporter assays, quantitative real time-polymerase chain reaction, Western blot, and TUNEL staining. Noteworthy, miR-155 was also found to be upregulated in the plasma of patients with septic cardiac dysfunction compared to sepsis patients without cardiac dysfunction, indicating a potential clinical relevance of miR-155. The receiver-operator characteristic curve indicated that plasma miR-155 might be a biomarker for sepsis patients developing cardiac dysfunction. Therefore, inhibition of miR-155 represents a novel therapy for septic myocardial dysfunction. Nature Publishing Group 2016-10 2016-10-11 /pmc/articles/PMC5095684/ /pubmed/27727247 http://dx.doi.org/10.1038/mtna.2016.80 Text en Copyright © 2016 Official journal of the American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wang, Hui Bei, Yihua Huang, Peipei Zhou, Qiulian Shi, Jing Sun, Qi Zhong, Jiuchang Li, Xinli Kong, Xiangqing Xiao, Junjie
spellingShingle	Wang, Hui Bei, Yihua Huang, Peipei Zhou, Qiulian Shi, Jing Sun, Qi Zhong, Jiuchang Li, Xinli Kong, Xiangqing Xiao, Junjie Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice
author_facet	Wang, Hui Bei, Yihua Huang, Peipei Zhou, Qiulian Shi, Jing Sun, Qi Zhong, Jiuchang Li, Xinli Kong, Xiangqing Xiao, Junjie
author_sort	Wang, Hui
title	Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice
title_short	Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice
title_full	Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice
title_fullStr	Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice
title_full_unstemmed	Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice
title_sort	inhibition of mir-155 protects against lps-induced cardiac dysfunction and apoptosis in mice
description	Sepsis-induced myocardial dysfunction represents a major cause of death in intensive care units. Dysregulated microRNAs (miR)-155 has been implicated in multiple cardiovascular diseases and miR-155 can be induced by lipopolysaccharide (LPS). However, the role of miR-155 in LPS-induced cardiac dysfunction is unclear. Septic cardiac dysfunction in mice was induced by intraperitoneal injection of LPS (5 mg/kg) and miR-155 was found to be significantly increased in heart challenged with LPS. Pharmacological inhibition of miR-155 using antagomiR improved cardiac function and suppressed cardiac apoptosis induced by LPS in mice as determined by echocardiography, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay, and Western blot for Bax and Bcl-2, while overexpression of miR-155 using agomiR had inverse effects. Pea15a was identified as a target gene of miR-155, mediating its effects in controlling apoptosis of cardiomyocytes as evidenced by luciferase reporter assays, quantitative real time-polymerase chain reaction, Western blot, and TUNEL staining. Noteworthy, miR-155 was also found to be upregulated in the plasma of patients with septic cardiac dysfunction compared to sepsis patients without cardiac dysfunction, indicating a potential clinical relevance of miR-155. The receiver-operator characteristic curve indicated that plasma miR-155 might be a biomarker for sepsis patients developing cardiac dysfunction. Therefore, inhibition of miR-155 represents a novel therapy for septic myocardial dysfunction.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095684/
_version_	1613713233180360704

Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice

Similar Items