Open AccessThe mechanical effects of CRT promoting autophagy via mitochondrial calcium uniporter down‐regulation and mitochondrial dynamics alteration
Author(s) -
Yu Ziqing,
Gong Xue,
Yu Yong,
Li Minghui,
Liang Yixiu,
Qin Shengmei,
Fulati Zibire,
Zhou Nianwei,
Shu Xianhong,
Nie Zhenning,
Dai Shimo,
Chen Xueying,
Wang Jingfeng,
Chen Ruizhen,
Su Yangang,
Ge Junbo
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14227
Subject(s) - autophagy , uniporter , microbiology and biotechnology , mitochondrion , angiotensin ii , cardiac fibrosis , medicine , autophagosome , heart failure , biology , chemistry , endocrinology , apoptosis , receptor , biochemistry , cytosol , enzyme
The mechanism of cardiac resynchronization therapy ( CRT ) remains unclear. In this study, mitochondria calcium uniporter ( MCU ), dynamin‐related protein‐1 ( DNM 1L/Drp1) and their relationship with autophagy in heart failure ( HF ) and CRT are investigated. Thirteen male beagle's dogs were divided into three groups (sham, HF , CRT ). Animals received left bundle branch ( LBB ) ablation followed by either 8‐week rapid atrial pacing or 4‐week rapid atrial pacing and 4‐week biventricular pacing. Cardiac function was evaluated by echocardiography. Differentially expressed genes ( DEG s) were detected by microarray analysis. General morphological changes, mitochondrial ultrastructure, autophagosomes and mitophagosomes were investigated. The cardiomyocyte stretching was adopted to imitate the mechanical effect of CRT . Cells were divided into three groups (control, angiotensin‐ II and angiotensin‐ II + stretching). MCU , DNM 1L/Drp1 and autophagy markers were detected by western blots or immunofluorescence. In the present study, CRT could correct cardiac dysfunction, decrease cardiomyocyte's size, alleviate cardiac fibrosis, promote the formation of autophagosome and mitigate mitochondrial injury. CRT significantly influenced gene expression profile, especially down‐regulating MCU and up‐regulating DNM 1L/Drp1. Cell stretching reversed the angiotensin‐ II induced changes of MCU and DNM 1L/Drp1 and partly restored autophagy. CRT 's mechanical effects down‐regulated MCU , up‐regulated DNM 1L/Drp1 and subsequently enhanced autophagy. Besides, the mechanical stretching prevented the angiotensin‐ II ‐induced cellular enlargement.