Loss of MD1 exacerbates pressure overload-induced left ventricular structural and electrical remodelling

Abstract Myeloid differentiation protein 1 (MD1) has been implicated in numerous pathophysiological processes, including immune regulation, obesity, insulin resistance, and inflammation. However, the role of MD1 in cardiac remodelling remains incompletely understood. We used MD1-knockout (KO) mice a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jianye Peng, Yu Liu, Xiaoju Xiong, Congxin Huang, Yang Mei, Zhiqiang Wang, Yanhong Tang, Jing Ye, Bin Kong, Wanli Liu, Teng Wang, He Huang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/78f4f0de2e7c4b4a84944dc3296482d3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:78f4f0de2e7c4b4a84944dc3296482d3
record_format	dspace
spelling	oai:doaj.org-article:78f4f0de2e7c4b4a84944dc3296482d32021-12-02T11:40:51ZLoss of MD1 exacerbates pressure overload-induced left ventricular structural and electrical remodelling10.1038/s41598-017-05379-w2045-2322https://doaj.org/article/78f4f0de2e7c4b4a84944dc3296482d32017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05379-whttps://doaj.org/toc/2045-2322Abstract Myeloid differentiation protein 1 (MD1) has been implicated in numerous pathophysiological processes, including immune regulation, obesity, insulin resistance, and inflammation. However, the role of MD1 in cardiac remodelling remains incompletely understood. We used MD1-knockout (KO) mice and their wild-type littermates to determine the functional significance of MD1 in the regulation of aortic banding (AB)-induced left ventricular (LV) structural and electrical remodelling and its underlying mechanisms. After 4 weeks of AB, MD1-KO hearts showed substantial aggravation of LV hypertrophy, fibrosis, LV dilation and dysfunction, and electrical remodelling, which resulted in overt heart failure and increased electrophysiological instability. Moreover, MD1-KO-AB cardiomyocytes showed increased diastolic sarcoplasmic reticulum (SR) Ca2+ leak, reduced Ca2+ transient amplitude and SR Ca2+ content, decreased SR Ca2+-ATPase2 expression, and increased phospholamban and Na+/Ca2+-exchanger 1 protein expression. Mechanistically, the adverse effects of MD1 deletion on LV remodelling were related to hyperactivated CaMKII signalling and increased impairment of intracellular Ca2+ homeostasis, whereas the increased electrophysiological instability was partly attributed to exaggerated prolongation of cardiac repolarisation, decreased action potential duration alternans threshold, and increased diastolic SR Ca2+ leak. Therefore, our study on MD1 could provide new therapeutic strategies for preventing/treating heart failure.Jianye PengYu LiuXiaoju XiongCongxin HuangYang MeiZhiqiang WangYanhong TangJing YeBin KongWanli LiuTeng WangHe HuangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jianye Peng Yu Liu Xiaoju Xiong Congxin Huang Yang Mei Zhiqiang Wang Yanhong Tang Jing Ye Bin Kong Wanli Liu Teng Wang He Huang Loss of MD1 exacerbates pressure overload-induced left ventricular structural and electrical remodelling
description	Abstract Myeloid differentiation protein 1 (MD1) has been implicated in numerous pathophysiological processes, including immune regulation, obesity, insulin resistance, and inflammation. However, the role of MD1 in cardiac remodelling remains incompletely understood. We used MD1-knockout (KO) mice and their wild-type littermates to determine the functional significance of MD1 in the regulation of aortic banding (AB)-induced left ventricular (LV) structural and electrical remodelling and its underlying mechanisms. After 4 weeks of AB, MD1-KO hearts showed substantial aggravation of LV hypertrophy, fibrosis, LV dilation and dysfunction, and electrical remodelling, which resulted in overt heart failure and increased electrophysiological instability. Moreover, MD1-KO-AB cardiomyocytes showed increased diastolic sarcoplasmic reticulum (SR) Ca2+ leak, reduced Ca2+ transient amplitude and SR Ca2+ content, decreased SR Ca2+-ATPase2 expression, and increased phospholamban and Na+/Ca2+-exchanger 1 protein expression. Mechanistically, the adverse effects of MD1 deletion on LV remodelling were related to hyperactivated CaMKII signalling and increased impairment of intracellular Ca2+ homeostasis, whereas the increased electrophysiological instability was partly attributed to exaggerated prolongation of cardiac repolarisation, decreased action potential duration alternans threshold, and increased diastolic SR Ca2+ leak. Therefore, our study on MD1 could provide new therapeutic strategies for preventing/treating heart failure.
format	article
author	Jianye Peng Yu Liu Xiaoju Xiong Congxin Huang Yang Mei Zhiqiang Wang Yanhong Tang Jing Ye Bin Kong Wanli Liu Teng Wang He Huang
author_facet	Jianye Peng Yu Liu Xiaoju Xiong Congxin Huang Yang Mei Zhiqiang Wang Yanhong Tang Jing Ye Bin Kong Wanli Liu Teng Wang He Huang
author_sort	Jianye Peng
title	Loss of MD1 exacerbates pressure overload-induced left ventricular structural and electrical remodelling
title_short	Loss of MD1 exacerbates pressure overload-induced left ventricular structural and electrical remodelling
title_full	Loss of MD1 exacerbates pressure overload-induced left ventricular structural and electrical remodelling
title_fullStr	Loss of MD1 exacerbates pressure overload-induced left ventricular structural and electrical remodelling
title_full_unstemmed	Loss of MD1 exacerbates pressure overload-induced left ventricular structural and electrical remodelling
title_sort	loss of md1 exacerbates pressure overload-induced left ventricular structural and electrical remodelling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/78f4f0de2e7c4b4a84944dc3296482d3
work_keys_str_mv	AT jianyepeng lossofmd1exacerbatespressureoverloadinducedleftventricularstructuralandelectricalremodelling AT yuliu lossofmd1exacerbatespressureoverloadinducedleftventricularstructuralandelectricalremodelling AT xiaojuxiong lossofmd1exacerbatespressureoverloadinducedleftventricularstructuralandelectricalremodelling AT congxinhuang lossofmd1exacerbatespressureoverloadinducedleftventricularstructuralandelectricalremodelling AT yangmei lossofmd1exacerbatespressureoverloadinducedleftventricularstructuralandelectricalremodelling AT zhiqiangwang lossofmd1exacerbatespressureoverloadinducedleftventricularstructuralandelectricalremodelling AT yanhongtang lossofmd1exacerbatespressureoverloadinducedleftventricularstructuralandelectricalremodelling AT jingye lossofmd1exacerbatespressureoverloadinducedleftventricularstructuralandelectricalremodelling AT binkong lossofmd1exacerbatespressureoverloadinducedleftventricularstructuralandelectricalremodelling AT wanliliu lossofmd1exacerbatespressureoverloadinducedleftventricularstructuralandelectricalremodelling AT tengwang lossofmd1exacerbatespressureoverloadinducedleftventricularstructuralandelectricalremodelling AT hehuang lossofmd1exacerbatespressureoverloadinducedleftventricularstructuralandelectricalremodelling
_version_	1718395524097245184

Loss of MD1 exacerbates pressure overload-induced left ventricular structural and electrical remodelling

Ejemplares similares