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学科主题临床医学
Ultrastructural uncoupling between T-tubules and sarcoplasmic reticulum in human heart failure
Zhang, Hai-Bo1; Li, Rong-Chang2; Xu, Ming3; Xu, Shi-Ming2; Lai, Ying-Si2; Wu, Hao-Di2; Xie, Xian-Jin4,5; Gao, Wei3; Ye, Haihong6; Zhang, You-Yi3; Meng, Xu1; Wang, Shi-Qiang2
关键词Heart Failure Myocardial Remodelling Ca-2 Signalling Excitation-contraction Coupling
刊名CARDIOVASCULAR RESEARCH
2013-05-01
DOI10.1093/cvr/cvt030
98期:2页:269-276
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems
研究领域[WOS]Cardiovascular System & Cardiology
关键词[WOS]CARDIAC-HYPERTROPHY ; RYANODINE RECEPTORS ; CA2+ RELEASE ; MYOCARDIAL-INFARCTION ; JUNCTOPHILIN TYPE-2 ; TRANSVERSE TUBULES ; HYPERTENSIVE RATS ; REDUCED SYNCHRONY ; FAILING HEARTS ; CALCIUM
英文摘要

Chronic heart failure is a complex clinical syndrome with impaired myocardial contractility. In failing cardiomyocytes, decreased signalling efficiency between the L-type Ca-2 channels (LCCs) in the plasma membrane (including transverse tubules, TTs) and the ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR) underlies the defective excitationcontraction (EC) coupling. It is therefore intriguing to know how the LCCRyR signalling apparatus is remodelled in human heart failure.

Stereological analysis of transmission electron microscopic images showed that the volume densities and the surface areas of TTs and junctional SRs were both decreased in heart failure specimens of dilated cardiomyopathy (DCM) and ischaemic cardiomyopathy (ICM). The TTSR junctions were reduced by 60, with the remaining displaced from the Z-line areas. Moreover, the spatial span of individual TTSR junctions was reduced by 17 in both DCM and ICM tissues. In accordance with these remodelling, junctophilin-2 (JP2), a structural protein anchoring SRs to TTs, was down-regulated, and miR-24, a microRNA that suppresses JP2 expression, was up-regulated in both heart failure tissues.

Human heart failure of distinct causes shared similar physical uncoupling between TTs and SRs, which appeared attributable to the reduced expression of JP2 and increased expression of miR-24. Therapeutic strategy against JP2 down-regulation would be expected to protect patients from cardiac EC uncoupling.

语种英语
WOS记录号WOS:000318575000015
项目编号2011CB809101 ; 30800475 ; 81070196 ; 30730013 ; 81030001 ; CITTCD20130339 ; 7132074
资助机构973 Major State Basic Research Development Program of China ; National Natural Science Foundation of China ; Program for New Century Excellent Talents in University ; Beijing Talents Foundation ; Importation and Development of High-Caliber Talents Project of Beijing Municipal Institutions ; Beijing Natural Science Foundation
引用统计
被引频次:33[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56954
专题北京大学第三临床医学院_心血管内科
作者单位1.Capital Med Univ, Beijing Anzhen Hosp, Beijing 100092, Peoples R China
2.Peking Univ, Coll Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China
3.Peking Univ, Hosp 3, Key Lab Mol Cardiovasc Sci, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Beijing 1000191, Peoples R China
4.Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA
5.Univ Texas SW Med Ctr Dallas, Simmons Canc Ctr, Dallas, TX 75390 USA
6.Capital Med Univ, Dept Med Genet, Beijing 100069, Peoples R China
推荐引用方式
GB/T 7714
Zhang, Hai-Bo,Li, Rong-Chang,Xu, Ming,et al. Ultrastructural uncoupling between T-tubules and sarcoplasmic reticulum in human heart failure[J]. CARDIOVASCULAR RESEARCH,2013,98(2):269-276.
APA Zhang, Hai-Bo.,Li, Rong-Chang.,Xu, Ming.,Xu, Shi-Ming.,Lai, Ying-Si.,...&Wang, Shi-Qiang.(2013).Ultrastructural uncoupling between T-tubules and sarcoplasmic reticulum in human heart failure.CARDIOVASCULAR RESEARCH,98(2),269-276.
MLA Zhang, Hai-Bo,et al."Ultrastructural uncoupling between T-tubules and sarcoplasmic reticulum in human heart failure".CARDIOVASCULAR RESEARCH 98.2(2013):269-276.
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