Loss of nuclear ARC contributes to the development of cardiac hypertrophy in rats

Aim Cardiac hypertrophy and myocardial apoptosis are two major factors in heart failure. As a classical regulator of apoptosis, apoptosis repressor with caspase recruitment domain (ARC) has recently also been found to have a protective effect against hypertrophy. However, the mechanism underlying th...

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Bibliographic Details
Published in:Acta Physiologica 2020-02, Vol.228 (2), p.e13337-n/a
Main Authors: Xie, Fang, Mei, Zhu‐Song, Wang, Xue, Zhang, Tao, Zhao, Yun, Wang, Shi‐Da, Qian, Ling‐Jia
Format: Article
Language:English
Subjects:
Angiotensin
Angiotensin II
Animal models
Apoptosis
ARC
cardiac hypertrophy
Caspase
Congestive heart failure
hypertension
Hypertrophy
Localization
Mass spectroscopy
Norepinephrine
nuclear localization
Nuclear transport
Prohibitin
Therapeutic applications
Transfection
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Summary:Aim Cardiac hypertrophy and myocardial apoptosis are two major factors in heart failure. As a classical regulator of apoptosis, apoptosis repressor with caspase recruitment domain (ARC) has recently also been found to have a protective effect against hypertrophy. However, the mechanism underlying this effect is still not fully understood. Methods In the present study, we established animal and cellular models to monitor the changes in total and nuclear ARC during cardiac hypertrophic processes. The preventive effects of nuclear ARC in cellular hypertrophy were verified by ARC regulation and nuclear export inhibition. To further explore the mechanism for nuclear ARC superficially, we analysed proteins that interact with ARC in the nucleus via Co‐IP and mass spectrometry. Results The expression of total ARC in hypertrophic myocardial tissue and H9C2 cells remained invariant, while the level of nuclear ARC decreased dramatically. By altering the content of ARC in H9C2 cells, we found that both nuclear ARC transfection and nuclear ARC export blockade attenuated norepinephrine or angiotensin II‐induced hypertrophy, while ARC knockdown had an inverse effect. Co‐IP data showed that ARC interacted with prohibitin (PHB) in the nucleus and might participate in maintaining the level of PHB in cells. Conclusions These findings suggest a novel mechanism for ARC in cardiac hypertrophy prevention and also indicate that the anti‐hypertrophic roles of ARC are probably associated with its localization in nucleus, which imply the nuclear ARC as a potential therapeutic target for cardiac hypertrophy.
ISSN:1748-1708
1748-1716
DOI:10.1111/apha.13337