Ang II Promotes Cardiac Autophagy and Hypertrophy via Orai1/STIM1

Chang-Bo Zheng; Wen-Cong Gao; Mingxu Xie; Zhichao Li; Xin Ma; Wencong Song; Dan Luo; Yongxiang Huang; Jichen Yang; Peng Zhang; Yu Huang; Weimin Yang; Xiaoqiang Yao

doi:10.3389/fphar.2021.622774

Ang II Promotes Cardiac Autophagy and Hypertrophy via Orai1/STIM1

Chang-Bo Zheng, Wen-Cong Gao, Mingxu Xie, Zhichao Li, Xin Ma, Wencong Song, Dan Luo, Yongxiang Huang, Jichen Yang, Peng Zhang, Yu Huang, Weimin Yang^*, Xiaoqiang Yao^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

23 Citations (Scopus)

49 Downloads (CityUHK Scholars)

Abstract

The pathophysiology of cardiac hypertrophy is complex and multifactorial. Both the store-operated Ca²⁺ entry (SOCE) and excessive autophagy are the major causative factors for pathological cardiac hypertrophy. However, it is unclear whether these two causative factors are interdependent. In this study, we examined the functional role of SOCE and Orai1 in angiotensin II (Ang II)-induced autophagy and hypertrophy using in vitro neonatal rat cardiomyocytes (NRCMs) and in vivo mouse model, respectively. We show that YM-58483 or SKF-96365 mediated pharmacological inhibition of SOCE, or silencing of Orai1 with Orail-siRNA inhibited Ang II-induced cardiomyocyte autophagy both in vitro and in vivo. Also, the knockdown of Orai1 attenuated Ang II-induced pathological cardiac hypertrophy. Together, these data suggest that Ang II promotes excessive cardiomyocyte autophagy through SOCE/Orai1 which can be the prime contributing factors in cardiac hypertrophy.

Original language	English
Article number	622774
Journal	Frontiers in Pharmacology
Volume	12
Online published	17 May 2021
DOIs	https://doi.org/10.3389/fphar.2021.622774
Publication status	Published - May 2021
Externally published	Yes

Research Keywords

angiotensin II
autophagy
Cardiac hypertrophy
orai1
SOCE
STIM1

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This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

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title = "Ang II Promotes Cardiac Autophagy and Hypertrophy via Orai1/STIM1",

abstract = "The pathophysiology of cardiac hypertrophy is complex and multifactorial. Both the store-operated Ca2+ entry (SOCE) and excessive autophagy are the major causative factors for pathological cardiac hypertrophy. However, it is unclear whether these two causative factors are interdependent. In this study, we examined the functional role of SOCE and Orai1 in angiotensin II (Ang II)-induced autophagy and hypertrophy using in vitro neonatal rat cardiomyocytes (NRCMs) and in vivo mouse model, respectively. We show that YM-58483 or SKF-96365 mediated pharmacological inhibition of SOCE, or silencing of Orai1 with Orail-siRNA inhibited Ang II-induced cardiomyocyte autophagy both in vitro and in vivo. Also, the knockdown of Orai1 attenuated Ang II-induced pathological cardiac hypertrophy. Together, these data suggest that Ang II promotes excessive cardiomyocyte autophagy through SOCE/Orai1 which can be the prime contributing factors in cardiac hypertrophy.",

keywords = "angiotensin II, autophagy, Cardiac hypertrophy, orai1, SOCE, STIM1",

author = "Chang-Bo Zheng and Wen-Cong Gao and Mingxu Xie and Zhichao Li and Xin Ma and Wencong Song and Dan Luo and Yongxiang Huang and Jichen Yang and Peng Zhang and Yu Huang and Weimin Yang and Xiaoqiang Yao",

year = "2021",

month = may,

doi = "10.3389/fphar.2021.622774",

language = "English",

volume = "12",

journal = "Frontiers in Pharmacology",

issn = "1663-9812",

publisher = "Frontiers Media S.A.",

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TY - JOUR

T1 - Ang II Promotes Cardiac Autophagy and Hypertrophy via Orai1/STIM1

AU - Zheng, Chang-Bo

AU - Gao, Wen-Cong

AU - Xie, Mingxu

AU - Li, Zhichao

AU - Ma, Xin

AU - Song, Wencong

AU - Luo, Dan

AU - Huang, Yongxiang

AU - Yang, Jichen

AU - Zhang, Peng

AU - Huang, Yu

AU - Yang, Weimin

AU - Yao, Xiaoqiang

PY - 2021/5

Y1 - 2021/5

N2 - The pathophysiology of cardiac hypertrophy is complex and multifactorial. Both the store-operated Ca2+ entry (SOCE) and excessive autophagy are the major causative factors for pathological cardiac hypertrophy. However, it is unclear whether these two causative factors are interdependent. In this study, we examined the functional role of SOCE and Orai1 in angiotensin II (Ang II)-induced autophagy and hypertrophy using in vitro neonatal rat cardiomyocytes (NRCMs) and in vivo mouse model, respectively. We show that YM-58483 or SKF-96365 mediated pharmacological inhibition of SOCE, or silencing of Orai1 with Orail-siRNA inhibited Ang II-induced cardiomyocyte autophagy both in vitro and in vivo. Also, the knockdown of Orai1 attenuated Ang II-induced pathological cardiac hypertrophy. Together, these data suggest that Ang II promotes excessive cardiomyocyte autophagy through SOCE/Orai1 which can be the prime contributing factors in cardiac hypertrophy.

AB - The pathophysiology of cardiac hypertrophy is complex and multifactorial. Both the store-operated Ca2+ entry (SOCE) and excessive autophagy are the major causative factors for pathological cardiac hypertrophy. However, it is unclear whether these two causative factors are interdependent. In this study, we examined the functional role of SOCE and Orai1 in angiotensin II (Ang II)-induced autophagy and hypertrophy using in vitro neonatal rat cardiomyocytes (NRCMs) and in vivo mouse model, respectively. We show that YM-58483 or SKF-96365 mediated pharmacological inhibition of SOCE, or silencing of Orai1 with Orail-siRNA inhibited Ang II-induced cardiomyocyte autophagy both in vitro and in vivo. Also, the knockdown of Orai1 attenuated Ang II-induced pathological cardiac hypertrophy. Together, these data suggest that Ang II promotes excessive cardiomyocyte autophagy through SOCE/Orai1 which can be the prime contributing factors in cardiac hypertrophy.

KW - angiotensin II

KW - autophagy

KW - Cardiac hypertrophy

KW - orai1

KW - SOCE

KW - STIM1

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UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85107201363&origin=recordpage

U2 - 10.3389/fphar.2021.622774

DO - 10.3389/fphar.2021.622774

M3 - RGC 21 - Publication in refereed journal

C2 - 34079454

SN - 1663-9812

VL - 12

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

M1 - 622774

ER -

Ang II Promotes Cardiac Autophagy and Hypertrophy via Orai1/STIM1

Abstract

Research Keywords

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Ang II Promotes Cardiac Autophagy and Hypertrophy via Orai1/STIM1

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