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Testosterone Prompted Cardiac Fibrosis in Arrhythmogenic Right Ventricular Cardiomyopathy: Evidence from Clinical to the in vitro Human iPSC-derived Engineered Cardiac Spheroids
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Hongyi Cheng, Xinrui Wang, Sichong Qian, Yike Zhang, Jincheng Jiao, Bingyu Zheng, Yue Zhu, Hua Xu, Jia Song, Feng Zhang, Xiaohong Jiang, Chang Cui, Minglong Chen. Testosterone Prompted Cardiac Fibrosis in Arrhythmogenic Right Ventricular Cardiomyopathy: Evidence from Clinical to the in vitro Human iPSC-derived Engineered Cardiac Spheroids[J]. Journal of Zhejiang University Science D, 2016, -1(-1): .
@article{title="Testosterone Prompted Cardiac Fibrosis in Arrhythmogenic Right Ventricular Cardiomyopathy: Evidence from Clinical to the in vitro Human iPSC-derived Engineered Cardiac Spheroids",
author="Hongyi Cheng, Xinrui Wang, Sichong Qian, Yike Zhang, Jincheng Jiao, Bingyu Zheng, Yue Zhu, Hua Xu, Jia Song, Feng Zhang, Xiaohong Jiang, Chang Cui, Minglong Chen",
journal="Journal of Zhejiang University Science D",
volume="-1",
number="-1",
pages="",
year="2016",
publisher="Zhejiang University Press & Springer",
doi="10.1007/s42242-BDMJ-D-24-00168"
}
%0 Journal Article
%T Testosterone Prompted Cardiac Fibrosis in Arrhythmogenic Right Ventricular Cardiomyopathy: Evidence from Clinical to the in vitro Human iPSC-derived Engineered Cardiac Spheroids
%A Hongyi Cheng
%A Xinrui Wang
%A Sichong Qian
%A Yike Zhang
%A Jincheng Jiao
%A Bingyu Zheng
%A Yue Zhu
%A Hua Xu
%A Jia Song
%A Feng Zhang
%A Xiaohong Jiang
%A Chang Cui
%A Minglong Chen
%J Journal of Zhejiang University SCIENCE D
%V -1
%N -1
%P
%@ 1673-1581
%D 2016
%I Zhejiang University Press & Springer
%DOI 10.1007/s42242-BDMJ-D-24-00168
TY - JOUR
T1 - Testosterone Prompted Cardiac Fibrosis in Arrhythmogenic Right Ventricular Cardiomyopathy: Evidence from Clinical to the in vitro Human iPSC-derived Engineered Cardiac Spheroids
A1 - Hongyi Cheng
A1 - Xinrui Wang
A1 - Sichong Qian
A1 - Yike Zhang
A1 - Jincheng Jiao
A1 - Bingyu Zheng
A1 - Yue Zhu
A1 - Hua Xu
A1 - Jia Song
A1 - Feng Zhang
A1 - Xiaohong Jiang
A1 - Chang Cui
A1 - Minglong Chen
J0 - Journal of Zhejiang University Science D
VL - -1
IS - -1
SP -
EP -
%@ 1673-1581
Y1 - 2016
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1007/s42242-BDMJ-D-24-00168
Abstract: Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a progressive disease characterized by adipose and fibrous replacement of the myocardium. Elevated testosterone levels may contribute to the pathological process in ARVC patients. However, the exact contribution of testosterone to cardiac fibrosis in ARVC remains unclear. In this study, we analyzed the gender Differences in the distribution of the low-voltage area in an ARVC cohort undergoing an electrophysiological study, and feature selection suggested the potential contribution of gender Differences in the low-voltage areas in ARVC patients. Additionally, we established engineered cardiac Spheroids models in vitro using patient-specific induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) and fibroblasts (icFBs), and elucidated the pathogenicity of abnormal splicing in the PKP2 gene caused by an intronic mutation. The additional pathogenic validation of the Desmoglein2 (DSG2) point mutation further confirms the reliability of the models. Moreover, testosterone exacerbated the DNA damage in the mutated cardiomyocytes (CMs) and further activated myofibroblasts as a chain reaction. In conclusion, we designed and constructed an in vitro 3D engineered cardiac spheroid model of ARVC based on clinical findings and provided direct evidence of the fibrotic role of testosterone in ARVC.
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