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Nitro-oleic acid enhances mitochondrial metabolism and ameliorates heart failure with preserved ejection fraction in mice

Author

Listed:
  • Marion Müller

    (Ruhr-Universität Bochum
    Ruhr-Universität Bochum)

  • Torben Schubert

    (Ruhr-Universität Bochum
    Ruhr-Universität Bochum)

  • Cornelius Welke

    (Ruhr-Universität Bochum
    Ruhr-Universität Bochum)

  • Tibor Maske

    (Ruhr-Universität Bochum
    Ruhr-Universität Bochum)

  • Thomas Patschkowski

    (Bielefeld University)

  • Elfi Donhauser

    (Ruhr-Universität Bochum
    Ruhr-Universität Bochum)

  • Jacqueline Heinen-Weiler

    (Ruhr-Universität Bochum)

  • Felix-Levin Hormann

    (Leibniz-Institut für Analytische Wissenschaften-ISAS e.V.)

  • Sven Heiles

    (Leibniz-Institut für Analytische Wissenschaften-ISAS e.V.
    University of Duisburg-Essen)

  • Tina Johanna Schulz

    (Ruhr-Universität Bochum
    Ruhr-Universität Bochum)

  • Luisa Andrea Lengenfelder

    (Ruhr-Universität Bochum
    Ruhr-Universität Bochum)

  • Lucia Landwehrjohann

    (Ruhr-Universität Bochum
    Ruhr-Universität Bochum)

  • Elisa Theres Vogt

    (Ruhr-Universität Bochum)

  • Bernd Stratmann

    (Ruhr-Universität Bochum)

  • Jurek Hense

    (University of Münster)

  • Simon Lüdtke

    (University of Münster)

  • Martina Düfer

    (University of Münster)

  • Elena Tolstik

    (Leibniz-Institut für Analytische Wissenschaften-ISAS e.V.)

  • Johann Dierks

    (Leibniz-Institut für Analytische Wissenschaften-ISAS e.V.)

  • Kristina Lorenz

    (Leibniz-Institut für Analytische Wissenschaften-ISAS e.V.
    University of Würzburg)

  • Tamino Huxohl

    (Ruhr-Universität Bochum)

  • Jan-Christian Reil

    (Ruhr-Universität Bochum)

  • Vasco Sequeira

    (DZHI)

  • Francisco Jose Schopfer

    (University of Pittsburgh)

  • Bruce A. Freeman

    (University of Pittsburgh)

  • Volker Rudolph

    (Ruhr-Universität Bochum
    Ruhr-Universität Bochum)

  • Uwe Schlomann

    (Ruhr-Universität Bochum
    Ruhr-Universität Bochum)

  • Anna Klinke

    (Ruhr-Universität Bochum
    Ruhr-Universität Bochum)

Abstract

The prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing, while treatment options are inadequate. Hypertension and obesity-related metabolic dysfunction contribute to HFpEF. Nitro-oleic acid (NO2-OA) impacts metabolic syndromes by improving glucose tolerance and adipocyte function. Here we show that treatment with NO2-OA ameliorates diastolic dysfunction and heart failure symptoms in a HFpEF mouse model induced by high-fat diet and inhibition of the endothelial nitric oxide synthase. Proteomic analysis of left ventricular tissue reveals that one-third of identified proteins, predominantly mitochondrial, are upregulated in hearts of NO2-OA-treated HFpEF mice compared to naïve and vehicle-treated HFpEF mice. Increased mitochondrial mass and numbers, and enhanced mitochondrial respiration are linked with this response, as assessed by transmission electron microscopy and high-resolution respirometry. Activation of the 5’-adenosine-monophosphate-activated-protein-kinase (AMPK) signaling pathway mediates the enhancement of mitochondrial dynamics in hearts of NO2-OA-treated HFpEF mice. These findings suggest that targeting mitochondrial function with NO2-OA may represent a promising therapeutic strategy for HFpEF.

Suggested Citation

  • Marion Müller & Torben Schubert & Cornelius Welke & Tibor Maske & Thomas Patschkowski & Elfi Donhauser & Jacqueline Heinen-Weiler & Felix-Levin Hormann & Sven Heiles & Tina Johanna Schulz & Luisa Andr, 2025. "Nitro-oleic acid enhances mitochondrial metabolism and ameliorates heart failure with preserved ejection fraction in mice," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59192-5
    DOI: 10.1038/s41467-025-59192-5
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    References listed on IDEAS

    as
    1. Gabriele G. Schiattarella & Francisco Altamirano & Dan Tong & Kristin M. French & Elisa Villalobos & Soo Young Kim & Xiang Luo & Nan Jiang & Herman I. May & Zhao V. Wang & Theodore M. Hill & Pradeep P, 2019. "Nitrosative stress drives heart failure with preserved ejection fraction," Nature, Nature, vol. 568(7752), pages 351-356, April.
    2. Gabriele G. Schiattarella & Francisco Altamirano & Soo Young Kim & Dan Tong & Anwarul Ferdous & Hande Piristine & Subhajit Dasgupta & Xuliang Wang & Kristin M. French & Elisa Villalobos & Stephen B. S, 2021. "Xbp1s-FoxO1 axis governs lipid accumulation and contractile performance in heart failure with preserved ejection fraction," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
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