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Exosomal microRNA-29a mediates cardiac dysfunction and mitochondrial inactivity in obesity-related cardiomyopathy

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Abstract

Purpose

Present study aims to explore the pathophysiological role of microRNA (miR)-29a in the process of obesity-related cardiomyopathy in human subjects and mice.

Methods

The expression level of circulating exosomal miR-29a was measured in 37 lean and 30 obese human subjects, and correlated with cardiac parameters. The effects of miR-29a on mitochondrial activity and cardiac function were investigated by treatment of miR-29a sponge in primary mouse cardiomyocytes and diet-induced obesity-related cardiomyopathy in mice.

Results

The increased circulating miR-29a level was closely associated with impaired human cardiac function, including ejection fraction (r = −0.2663, p < 0.05) and NT-proBNP levels (r = 0.4270, p < 0.001). Exosomes from obese human plasma mediated cardiomyocyte mitochondrial inactivity, but pre-treatment with miR-29a sponge attenuated the exosomal miR-29a-induced reduction of ATP production (p < 0.001), basal oxygen consumption (p < 0.01) and mitochondrial complex I activity (p < 0.01). In vivo mouse study, high fat diet damaged cardiac function, normal structure, and mitochondrial activity, whereas miR-29a sponge improved the cardiac status.

Conclusions

Present study uncovered the correlation between circulating miR-29a and cardiac parameters in human subjects, and provided solid evidence of the therapeutic application of miR-29a sponge in combating obesity-mediated cardiac dysfunction.

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Acknowledgements

This study was supported by the match funding for the Key Laboratory of Myocardial Ischemia, Chinese Ministry Education (KL201316), The Heilongjiang Postdoctoral Fund (LBH-Z16133), and Chinese Postdoctoral Science Foundation (2017M611395).

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    Authors and Affiliations

    1. Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China

      Fengqin Li, Ting Xu, Wenjuan Du, Bo Yu, Youbin Liu & Honggang Nie

    2. Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China

      Kuikui Zhang

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    1. Fengqin Li
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    Correspondence to Youbin Liu or Honggang Nie.

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    These authors contributed equally: Fengqin Li, Kuikui Zhang.

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    Li, F., Zhang, K., Xu, T. et al. Exosomal microRNA-29a mediates cardiac dysfunction and mitochondrial inactivity in obesity-related cardiomyopathy. Endocrine 63, 480–488 (2019). https://doi.org/10.1007/s12020-018-1753-7

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