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Suppression of angiopoietin-like 4 reprograms endothelial cell metabolism and inhibits angiogenesis

Author

Listed:
  • Balkrishna Chaube

    (Yale University School of Medicine
    Yale University School of Medicine
    Yale University School of Medicine)

  • Kathryn M. Citrin

    (Yale University School of Medicine
    Yale University School of Medicine
    Yale University School of Medicine
    Yale University)

  • Mahnaz Sahraei

    (Yale University School of Medicine)

  • Abhishek K. Singh

    (Yale University School of Medicine
    Yale University School of Medicine)

  • Diego Saenz Urturi

    (Yale University School of Medicine
    Yale University School of Medicine
    Yale University School of Medicine)

  • Wen Ding

    (Yale University School of Medicine)

  • Richard W. Pierce

    (Yale University School of Medicine
    Yale University School of Medicine)

  • Raaisa Raaisa

    (Yale University)

  • Rebecca Cardone

    (Yale University)

  • Richard Kibbey

    (Yale University School of Medicine
    Yale University
    Yale University)

  • Carlos Fernández-Hernando

    (Yale University School of Medicine
    Yale University School of Medicine
    Yale University School of Medicine
    Yale University School of Medicine)

  • Yajaira Suárez

    (Yale University School of Medicine
    Yale University School of Medicine
    Yale University School of Medicine
    Yale University School of Medicine)

Abstract

Angiopoietin-like 4 (ANGPTL4) is known to regulate various cellular and systemic functions. However, its cell-specific role in endothelial cells (ECs) function and metabolic homeostasis remains to be elucidated. Here, using endothelial-specific Angptl4 knock-out mice (Angptl4iΔEC), and transcriptomics and metabolic flux analysis, we demonstrate that ANGPTL4 is required for maintaining EC metabolic function vital for vascular permeability and angiogenesis. Knockdown of ANGPTL4 in ECs promotes lipase-mediated lipoprotein lipolysis, which results in increased fatty acid (FA) uptake and oxidation. This is also paralleled by a decrease in proper glucose utilization for angiogenic activation of ECs. Mice with endothelial-specific deletion of Angptl4 showed decreased pathological neovascularization with stable vessel structures characterized by increased pericyte coverage and reduced permeability. Together, our study denotes the role of endothelial-ANGPTL4 in regulating cellular metabolism and angiogenic functions of EC.

Suggested Citation

  • Balkrishna Chaube & Kathryn M. Citrin & Mahnaz Sahraei & Abhishek K. Singh & Diego Saenz Urturi & Wen Ding & Richard W. Pierce & Raaisa Raaisa & Rebecca Cardone & Richard Kibbey & Carlos Fernández-Her, 2023. "Suppression of angiopoietin-like 4 reprograms endothelial cell metabolism and inhibits angiogenesis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43900-0
    DOI: 10.1038/s41467-023-43900-0
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    1. Yin Li & Manling Jiang & Ling Aye & Li Luo & Yong Zhang & Fengkai Xu & Yongqi Wei & Dan Peng & Xiang He & Jie Gu & Xiaofang Yu & Guoping Li & Di Ge & Chunlai Lu, 2024. "UPP1 promotes lung adenocarcinoma progression through the induction of an immunosuppressive microenvironment," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

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