IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43900-0.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43900-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43900-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Pengchun Yu & Kerstin Wilhelm & Alexandre Dubrac & Joe K. Tung & Tiago C. Alves & Jennifer S. Fang & Yi Xie & Jie Zhu & Zehua Chen & Frederik De Smet & Jiasheng Zhang & Suk-Won Jin & Lele Sun & Hongye, 2017. "FGF-dependent metabolic control of vascular development," Nature, Nature, vol. 545(7653), pages 224-228, May.
    2. Peter Carmeliet & Rakesh K. Jain, 2011. "Molecular mechanisms and clinical applications of angiogenesis," Nature, Nature, vol. 473(7347), pages 298-307, May.
    3. Sandra Schoors & Ulrike Bruning & Rindert Missiaen & Karla C. S. Queiroz & Gitte Borgers & Ilaria Elia & Annalisa Zecchin & Anna Rita Cantelmo & Stefan Christen & Jermaine Goveia & Ward Heggermont & L, 2015. "Fatty acid carbon is essential for dNTP synthesis in endothelial cells," Nature, Nature, vol. 520(7546), pages 192-197, April.
    4. Kerstin Wilhelm & Katharina Happel & Guy Eelen & Sandra Schoors & Mark F. Oellerich & Radiance Lim & Barbara Zimmermann & Irene M. Aspalter & Claudio A. Franco & Thomas Boettger & Thomas Braun & Marcu, 2016. "FOXO1 couples metabolic activity and growth state in the vascular endothelium," Nature, Nature, vol. 529(7585), pages 216-220, January.
    5. George D. Yancopoulos & Samuel Davis & Nicholas W. Gale & John S. Rudge & Stanley J. Wiegand & Jocelyn Holash, 2000. "Vascular-specific growth factors and blood vessel formation," Nature, Nature, vol. 407(6801), pages 242-248, September.
    6. Felipe Slebe & Federico Rojo & Maria Vinaixa & Mar García-Rocha & Giorgia Testoni & Marc Guiu & Evarist Planet & Sara Samino & Enrique J. Arenas & Antoni Beltran & Ana Rovira & Ana Lluch & Xavier Salv, 2016. "FoxA and LIPG endothelial lipase control the uptake of extracellular lipids for breast cancer growth," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    7. Sandra Schoors & Ulrike Bruning & Rindert Missiaen & Karla C. S. Queiroz & Gitte Borgers & Ilaria Elia & Annalisa Zecchin & Anna Rita Cantelmo & Stefan Christen & Jermaine Goveia & Ward Heggermont & L, 2015. "Correction: Corrigendum: Fatty acid carbon is essential for dNTP synthesis in endothelial cells," Nature, Nature, vol. 526(7571), pages 144-144, October.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Nieves Montenegro-Navarro & Claudia García-Báez & Melissa García-Caballero, 2023. "Molecular and metabolic orchestration of the lymphatic vasculature in physiology and pathology," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Odeta Meçe & Diede Houbaert & Maria-Livia Sassano & Tania Durré & Hannelore Maes & Marco Schaaf & Sanket More & Maarten Ganne & Melissa García-Caballero & Mila Borri & Jelle Verhoeven & Madhur Agrawal, 2022. "Lipid droplet degradation by autophagy connects mitochondria metabolism to Prox1-driven expression of lymphatic genes and lymphangiogenesis," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Ling Tao & Mahmoud A. Mohammad & Giorgio Milazzo & Myrthala Moreno-Smith & Tajhal D. Patel & Barry Zorman & Andrew Badachhape & Blanca E. Hernandez & Amber B. Wolf & Zihua Zeng & Jennifer H. Foster & , 2022. "MYCN-driven fatty acid uptake is a metabolic vulnerability in neuroblastoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Vincent Geldhof & Laura P. M. H. Rooij & Liliana Sokol & Jacob Amersfoort & Maxim Schepper & Katerina Rohlenova & Griet Hoste & Adriaan Vanderstichele & Anne-Marie Delsupehe & Edoardo Isnaldi & Naima , 2022. "Single cell atlas identifies lipid-processing and immunomodulatory endothelial cells in healthy and malignant breast," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    5. Anastasiya Strembitska & Gwenaël Labouèbe & Alexandre Picard & Xavier P. Berney & David Tarussio & Maxime Jan & Bernard Thorens, 2022. "Lipid biosynthesis enzyme Agpat5 in AgRP-neurons is required for insulin-induced hypoglycemia sensing and glucagon secretion," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Anna Goussia & Nafsika Simou & Flora Zagouri & Kyriaki Manousou & Georgios Lazaridis & Helen Gogas & Angelos Koutras & Maria Sotiropoulou & George Pentheroudakis & Dimitrios Bafaloukos & Christos Mark, 2018. "Associations of angiogenesis-related proteins with specific prognostic factors, breast cancer subtypes and survival outcome in early-stage breast cancer patients. A Hellenic Cooperative Oncology Group," PLOS ONE, Public Library of Science, vol. 13(7), pages 1-19, July.
    7. Zongchao Sun & Likun Yang & Abdukahar Kiram & Jing Yang & Zhuangzhuang Yang & Liwei Xiao & Yujing Yin & Jing Liu & Yan Mao & Danxia Zhou & Hao Yu & Zheng Zhou & Dengqiu Xu & Yuhuan Jia & Chenyun Ding , 2023. "FNIP1 abrogation promotes functional revascularization of ischemic skeletal muscle by driving macrophage recruitment," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. Fabian Peisker & Maurice Halder & James Nagai & Susanne Ziegler & Nadine Kaesler & Konrad Hoeft & Ronghui Li & Eric M. J. Bindels & Christoph Kuppe & Julia Moellmann & Michael Lehrke & Christian Stopp, 2022. "Mapping the cardiac vascular niche in heart failure," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    9. Eun-A Kwak & Christopher C. Pan & Aaron Ramonett & Sanjay Kumar & Paola Cruz-Flores & Tasmia Ahmed & Hannah R. Ortiz & Jeffrey J. Lochhead & Nathan A. Ellis & Ghassan Mouneimne & Teodora G. Georgieva , 2022. "βIV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    10. Silje Kjølle & Kenneth Finne & Even Birkeland & Vandana Ardawatia & Ingeborg Winge & Sura Aziz & Gøril Knutsvik & Elisabeth Wik & Joao A. Paulo & Heidrun Vethe & Dimitrios Kleftogiannis & Lars A. Aksl, 2023. "Hypoxia induced responses are reflected in the stromal proteome of breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    11. Domanskyi, Sergii & Hakansson, Alex & Meng, Michelle & Pham, Benjamin K & Graff Zivin, Joshua S & Piermarocchi, Carlo & Paternostro, Giovanni & Ferrara, Napoleone, 2022. "Naturally occurring combinations of receptors from single cell transcriptomics in endothelial cells," University of California at San Diego, Economics Working Paper Series qt7rx412x7, Department of Economics, UC San Diego.
    12. Gianna Maria Nardi & Elisabetta Ferrara & Ilaria Converti & Francesca Cesarano & Salvatore Scacco & Roberta Grassi & Antonio Gnoni & Felice Roberto Grassi & Biagio Rapone, 2020. "Does Diabetes Induce the Vascular Endothelial Growth Factor (VEGF) Expression in Periodontal Tissues? A Systematic Review," IJERPH, MDPI, vol. 17(8), pages 1-16, April.
    13. Shilpa Bhatia & Diemmy Nguyen & Laurel B. Darragh & Benjamin Van Court & Jaspreet Sharma & Michael W. Knitz & Miles Piper & Sanjana Bukkapatnam & Jacob Gadwa & Thomas E. Bickett & Shiv Bhuvane & Sophi, 2022. "EphB4 and ephrinB2 act in opposition in the head and neck tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    14. Jaco Selle & Katharina Dinger & Vanessa Jentgen & Daniela Zanetti & Johannes Will & Theodoros Georgomanolis & Christina Vohlen & Rebecca Wilke & Baktybek Kojonazarov & Oleksiy Klymenko & Jasmine Mohr , 2022. "Maternal and perinatal obesity induce bronchial obstruction and pulmonary hypertension via IL-6-FoxO1-axis in later life," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    15. Haifeng Zhang & Busu Li & Qunhua Huang & Francesc López-Giráldez & Yoshiaki Tanaka & Qun Lin & Sameet Mehta & Guilin Wang & Morven Graham & Xinran Liu & In-Hyun Park & Anne Eichmann & Wang Min & Jenny, 2022. "Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    16. Mariafrancesca Cascione & Valeria De Matteis & Rosaria Rinaldi, 2019. "Cytomechanical Alterations Induced by Inorganic NPs," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 14(4), pages 1-2, February.
    17. Cristiana Spinelli & Lata Adnani & Brian Meehan & Laura Montermini & Sidong Huang & Minjun Kim & Tamiko Nishimura & Sidney E. Croul & Ichiro Nakano & Yasser Riazalhosseini & Janusz Rak, 2024. "Mesenchymal glioma stem cells trigger vasectasia—distinct neovascularization process stimulated by extracellular vesicles carrying EGFR," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    18. Sara G. Romeo & Ilaria Secco & Edoardo Schneider & Christina M. Reumiller & Celio X. C. Santos & Anna Zoccarato & Vishal Musale & Aman Pooni & Xiaoke Yin & Konstantinos Theofilatos & Silvia Cellone Tr, 2023. "Human blood vessel organoids reveal a critical role for CTGF in maintaining microvascular integrity," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43900-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.