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The metabolic engine of endothelial cells

Nature Metabolism volume 1, pages 937–946 (2019)Cite this article

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Abstract

Endothelial cells (ECs) line the quiescent vasculature but can form new blood vessels (a process termed angiogenesis) in disease. Strategies targeting angiogenic growth factors have been clinically developed for the treatment of malignant and ocular diseases. Studies over the past decade have documented that several pathways of central carbon metabolism are necessary for EC homeostasis and growth, and that strategies that stimulate or block EC metabolism can be used to promote or inhibit vessel growth, respectively. In this Review, we provide an updated overview of the growing understanding of central carbon metabolic pathways in ECs and the therapeutic opportunities for targeting EC metabolism.

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Fig. 1: ECs rely on metabolic rewiring for angiogenesis.
Fig. 2: Key metabolic pathways in ECs.
Fig. 3: Adaptations of metabolic pathways in quiescent versus angiogenic ECs.
Fig. 4: Adaptations of metabolic pathways in lymphatic ECs.
Fig. 5: Amino acid metabolism in angiogenic ECs.
Fig. 6: Therapeutic strategies targeting EC metabolism.

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Acknowledgements

The authors thank all laboratory members, colleagues and collaborators for contributing to the discussed data. K.D.F. is supported by a Marie Sklodowska-Curie IF (H2020-MSCA-IF-2017, No. 799522). K.R. is supported by the Research Foundation Flanders (FWO, grant no. 12V9318N). Y.L. is supported by Sanming Project of Medicine in Shenzhen (SZSM201612074), BGI-Research, the Danish Research Council for Independent Research (DFF–1337–00128), a Sapere Aude Young Research Talent Prize (DFF-1335–00763A) and an Aarhus University Strategic Grant (AU-iCRISPR). The work of P.C. is supported by the VIB TechWatch program, long-term structural Methusalem funding by the Flemish Government, the Research Foundation Flanders (FWO-Vlaanderen), the Foundation Against Cancer (grant no. 2016–078), and European Research Council (ERC) Proof-of-concept (ERC-713758) and Advanced Research Grant (EU-ERC743074).

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Authors and Affiliations

  1. Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, Leuven, Belgium

    Kim D. Falkenberg, Katerina Rohlenova & Peter Carmeliet

  2. Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium

    Kim D. Falkenberg, Katerina Rohlenova & Peter Carmeliet

  3. Lars Bolund Institute of Regenerative Medicine, BGI-Qindao, Qindao, China

    Yonglun Luo

  4. Department of Biomedicine, Aarhus University, Aarhus, Denmark

    Yonglun Luo

  5. BGI-Shenzhen, Shenzhen, China

    Yonglun Luo

  6. China National GeneBank, BGI-Shenzhen, Shenzhen, China

    Yonglun Luo

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All authors prepared, revised the manuscript and approved the final version; K.D.F. prepared the figures.

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Correspondence to Peter Carmeliet.

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Falkenberg, K.D., Rohlenova, K., Luo, Y. et al. The metabolic engine of endothelial cells. Nat Metab 1, 937–946 (2019). https://doi.org/10.1038/s42255-019-0117-9

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