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Disruption of mindin exacerbates cardiac hypertrophy and fibrosis

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An Erratum to this article was published on 30 August 2017

Abstract

Cardiac hypertrophy is a response of the myocardium to increased workload and is characterised by an increase of myocardial mass and an accumulation of extracellular matrix (ECM). As an ECM protein, an integrin ligand, and an angiogenesis inhibitor, all of which are key players in cardiac hypertrophy, mindin is an attractive target for therapeutic intervention to treat or prevent cardiac hypertrophy and heart failure. In this study, we investigated the role of mindin in cardiac hypertrophy using littermate Mindin knockout (Mindin −/−) and wild-type (WT) mice. Cardiac hypertrophy was induced by aortic banding (AB) or angiotensin II (Ang II) infusion in Mindin −/− and WT mice. The extent of cardiac hypertrophy was quantitated by echocardiography and by pathological and molecular analyses of heart samples. Mindin −/− mice were more susceptible to cardiac hypertrophy and fibrosis in response to AB or Ang II stimulation than wild type. Cardiac function was also markedly exacerbated during both systole and diastole in Mindin −/− mice in response to hypertrophic stimuli. Western blot assays further showed that the activation of AKT/glycogen synthase kinase 3β (GSK3β) signalling in response to hypertrophic stimuli was significantly increased in Mindin −/− mice. Moreover, blocking AKT/GSK3β signalling with a pharmacological AKT inhibitor reversed cardiac abnormalities in Mindin −/− mice. Our data show that mindin, as an intrinsic cardioprotective factor, prevents maladaptive remodelling and the transition to heart failure by blocking AKT/GSK3β signalling.

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Acknowledgements and disclosure statement

This research was supported by the National Natural Science Foundation of China (grants 30900524, 30972954, 81000036 and 81000095) the Support Program for Disciplinary Leaders in Wuhan (200951830561), the Fundamental Research Funds for the Central Universities (3081013) and the National Basic Research Program of China (grant 2011CB503902).

Conflicts of interest

The authors have declared that no conflict of interest exists.

Author information

Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, JieFang Road 238, Wuhan, 430060, People’s Republic of China

    Zhou-Yan Bian, Qi-Zhu Tang, Jinghua Feng, Yan Zhang, Ding-Sheng Jiang, Ling Yan & Hongliang Li

  2. Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, People’s Republic of China

    Zhou-Yan Bian, Qi-Zhu Tang, Jinghua Feng, Yan Zhang, Ding-Sheng Jiang, Ling Yan & Hongliang Li

  3. Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Xiang Wei

  4. Department of Cardiology, Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Shan Deng

  5. Department of Cardiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    Chen Liu

  6. Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China

    Lian-Feng Zhang

  7. Division of Cardiology, Heart and Stroke/Richard Lewar Centre of Excellence. University Health Network, University of Toronto, Ontario, M5S3E2, Canada

    Manyin Chen & Peter P. Liu

  8. Cardiovascular Division, University of Minnesota, Minneapolis, MN, 55455, USA

    John Fassett & Yingjie Chen

  9. Department of Immunology, Duke University Medical Center, Durham, NC, 27710, USA

    You-Wen He

  10. Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, 35294-3360, USA

    Qinglin Yang

Authors
  1. Zhou-Yan Bian
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  2. Xiang Wei
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  3. Shan Deng
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  6. Yan Zhang
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  15. Qinglin Yang
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  16. Peter P. Liu
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  17. Hongliang Li
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Corresponding author

Correspondence to Hongliang Li.

Additional information

Bian Zhou-Yan, Xiang Wei and Shan Deng are as co-first authors.

An erratum to this article is available at http://dx.doi.org/10.1007/s00109-017-1588-3.

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Bian, ZY., Wei, X., Deng, S. et al. Disruption of mindin exacerbates cardiac hypertrophy and fibrosis. J Mol Med 90, 895–910 (2012). https://doi.org/10.1007/s00109-012-0883-2

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  • DOI: https://doi.org/10.1007/s00109-012-0883-2

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