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Published Online: 6 October 2014

Overexpression of Mitofilin in the Mouse Heart Promotes Cardiac Hypertrophy in Response to Hypertrophic Stimuli

Publication: Antioxidants & Redox Signaling
Volume 21, Issue Number 12

Abstract

Aims: Mitofilin was originally described as a heart muscle protein because of its abundance in the heart tissue; however, its function in the heart is still to be elucidated. Thus, this study aims at investigating the role of mitofilin in the heart in response to hypertrophic stimuli. Results: In this study, a significant increase in mitofilin expression was observed in the hearts of patients with hypertrophic cardiomyopathy. Transgenic (TG) mice with cardiomyocyte-specific overexpression of mitofilin were generated, and cardiac hypertrophy was introduced by transverse aortic constriction (TAC) or chronic infusion of isoproterenol (ISO). In TG mice overexpressing mitofilin, the level of cardiac hypertrophy was significantly greater than that in wild-type (WT) mice after TAC and ISO stimulation. A detailed analysis showed that compared with WT mice, the level of reactive oxygen species was increased after TAC and ISO induction and mitochondrial oxidative phosphorylation (OXPHOS) activity in the TG hearts was lower. These alterations may contribute to the aggravated cardiac hypertrophy observed in response to TAC and ISO stimulation. Conclusion: Over-expression of mitofilin promotes cardiac hypertrophy under pathological conditions both in vivo and in vitro. Innovation: Mitofilin, a mitochondria protein, is shown to be related to cardiac hypertrophy for the first time, which enhances our understanding of the role of mitochondria in cardiac hypertrophy. Antioxid. Redox Signal. 21, 1693–1707

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Information & Authors

Information

Published In

cover image Antioxidants & Redox Signaling
Antioxidants & Redox Signaling
Volume 21Issue Number 12October 20, 2014
Pages: 1693 - 1707
PubMed: 24555791

History

Published in print: October 20, 2014
Published online: 6 October 2014
Published ahead of print: 2 May 2014
Published ahead of production: 20 February 2014
Accepted: 20 February 2014
Revision received: 28 January 2014
Received: 5 June 2013

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    Authors

    Affiliations

    Yuan Zhang
    *
    State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.
    Jing Xu*
    State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.
    Yu-Xuan Luo
    State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.
    Xi-Zhou An
    State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.
    Ran Zhang
    State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.
    Guang Liu
    State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.
    Hongliang Li
    Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
    Hou-Zao Chen
    State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.
    De-Pei Liu
    State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.

    Notes

    Address correspondence to:Dr. De-Pei LiuState Key Laboratory of Medical Molecular BiologyDepartment of Biochemistry and Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100005People's Republic of China
    E-mail: [email protected]
    Dr. Hou-Zao ChenState Key Laboratory of Medical Molecular BiologyDepartment of Biochemistry and Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100005People's Republic of China
    E-mail: [email protected]

    Author Disclosure Statement

    No competing financial interests exist.

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