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GLP-1 Improves Diastolic Function and Survival in Heart Failure with Preserved Ejection Fraction

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Abstract

Heart failure with preserved ejection fraction (HFpEF) has emerged as a public health burden with currently no effective medication. We assessed the treatment effects of the incretin hormone glucagon-like peptide-1 (GLP-1) on cardiac metabolism and function in a model of HFpEF. Following aortic banding, rats developed HFpEF characterized by diastolic dysfunction, pulmonary congestion, and poor survival (38%). A 4-week GLP-1 treatment via osmotic pumps significantly improved survival (70%) and reduced left ventricular stiffness, diastolic dysfunction, and pulmonary congestion. Isolated heart perfusion revealed preserved cardiac glucose oxidation (GO) and a shift in cardiac substrate utilization towards GO. While GLP-1 may boost insulin secretion and responsiveness, the protective effects were not related to cardiac insulin action. GLP-1 improves diastolic function and survival in rats with HFpEF, which was associated with a cardiac substrate switch towards GO. The therapeutic role of GLP-1 in HFpEF is new and warrants further investigation.

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Funding

This study was supported by grants of the Novartis-Stiftung für Therapeutische Forschung and the DFG (Deutsche Forschungsgemeinschaft).

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747, Jena, Germany

    T. Dung Nguyen, Paulo A. Amorim, Christina Schenkl, Michael Schwarzer & Torsten Doenst

  2. Department of Cardiovascular and Thoracic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan

    Yasushige Shingu

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  1. T. Dung Nguyen
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  2. Yasushige Shingu
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  3. Paulo A. Amorim
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  4. Christina Schenkl
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  6. Torsten Doenst
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Correspondence to Torsten Doenst.

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The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The experimental protocols were approved by the responsible Institutional Animal Care and Use Committee.

This article does not contain any studies with human participants performed by any of the authors.

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Associate Editor Saptarsi Haldar oversaw the review of this article

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Nguyen, T.D., Shingu, Y., Amorim, P.A. et al. GLP-1 Improves Diastolic Function and Survival in Heart Failure with Preserved Ejection Fraction. J. of Cardiovasc. Trans. Res. 11, 259–267 (2018). https://doi.org/10.1007/s12265-018-9795-z

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  • DOI: https://doi.org/10.1007/s12265-018-9795-z

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