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<p>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 (NO<sub>2</sub>-OA) impacts metabolic syndromes by improving glucose tolerance and adipocyte function. Here we show that treatment with NO<sub>2</sub>-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 NO<sub>2</sub>-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 NO<sub>2</sub>-OA-treated HFpEF mice. These findings suggest that targeting mitochondrial function with NO<sub>2</sub>-OA may represent a promising therapeutic strategy for HFpEF.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月26日

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  • Marion Müller,
  • Torben Schubert,
  • Cornelius Welke,
  • Tibor Maske,
  • Thomas Patschkowski,
  • Elfi Donhauser,
  • Jacqueline Heinen-Weiler,
  • Felix-Levin Hormann,
  • Sven Heiles,
  • Tina Johanna Schulz,
  • Luisa Andrea Lengenfelder,
  • Lucia Landwehrjohann,
  • Elisa Theres Vogt,
  • Bernd Stratmann,
  • Jurek Hense,
  • Simon Lüdtke,
  • Martina Düfer,
  • Elena Tolstik,
  • Johann Dierks,
  • Kristina Lorenz,
  • Tamino Huxohl,
  • Jan-Christian Reil,
  • Vasco Sequeira,
  • Francisco Jose Schopfer,
  • Bruce A. Freeman,
  • Volker Rudolph,
  • Uwe Schlomann,
  • Anna Klinke

摘要

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.