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Cited by 192Cholesterol and Lipid MetabolismAngiogenesis and VEGF in CancerCancer, Lipids, and Metabolism

Control of angiogenesis by AIBP-mediated cholesterol efflux

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Fang, Longhou, Choi, Soo-Ho, Baek, Ji Sun, Liu, Chao, Almazan, Felicidad, Ulrich, Florian, Wiesner, Philipp, Taleb, Adam +5 more·2013·Nature
DOI 10.1038/nature12166PMC PMC3760669
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Abstract

Cholesterol is a structural component of the cell and is indispensable for normal cellular function, although its excess often leads to abnormal proliferation, migration, inflammatory responses and/or cell death. To prevent cholesterol overload, ATP-binding cassette (ABC) transporters mediate cholesterol efflux from the cells to apolipoprotein A-I (apoA-I) and the apoA-I-containing high-density lipoprotein (HDL). Maintaining efficient cholesterol efflux is essential for normal cellular function. However, the role of cholesterol efflux in angiogenesis and the identity of its local regulators are poorly understood. Here we show that apoA-I binding protein (AIBP) accelerates cholesterol efflux from endothelial cells to HDL and thereby regulates angiogenesis. AIBP- and HDL-mediated cholesterol depletion reduces lipid rafts, interferes with VEGFR2 (also known as KDR) dimerization and signalling and inhibits vascular endothelial growth factor-induced angiogenesis in vitro and mouse aortic neovascularization ex vivo. Notably, Aibp, a zebrafish homologue of human AIBP, regulates the membrane lipid order in embryonic zebrafish vasculature and functions as a non-cell-autonomous regulator of angiogenesis. aibp knockdown results in dysregulated sprouting/branching angiogenesis, whereas forced Aibp expression inhibits angiogenesis. Dysregulated angiogenesis is phenocopied in Abca1 (also known as Abca1a) Abcg1-deficient embryos, and cholesterol levels are increased in Aibp-deficient and Abca1 Abcg1-deficient embryos. Our findings demonstrate that secreted AIBP positively regulates cholesterol efflux from endothelial cells and that effective cholesterol efflux is critical for proper angiogenesis.

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Cited by

Sorted by citations

Authors
Fang, L., Choi, S.-H., Baek, J. S., Liu, C., Almazan, F., Ulrich, F., Wiesner, P., Taleb, A., Deer, E., Pattison, J., Torres-Vázquez, J., Li, A. C., & Miller, Y. I.
Affiliations
  • University of California San Diego (US)
  • NYU Langone Health (US)
Corresponding author
Miller, Yury I.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2013-05-29
Volume
498
Issue
7452
Pages
118-122
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature12166
PMC
PMC3760669
OpenAlex
W2052849118
Cited by
192
References
0
Citations by year
2026: 12 · 2025: 12 · 2024: 19 · 2023: 9 · 2022: 12 · 2021: 15 · 2020: 22 · 2019: 12 · 2018: 14 · 2017: 18 · 2016: 13 · 2015: 15 · 2014: 13 · 2013: 5
FWCI
15.13
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Heart, Lung, and Blood Institute (HL-055798, HL093767, R01HL093767, R00HL114734, P01HL055798, P01HL088093, HL114734, K99HL114734, R01HL092263)
  • National Institute of Neurological Disorders and Stroke (P30NS047101)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
angiogenesis, cholesterol efflux, high-density lipoprotein, endothelial cells, lipid rafts, membrane order, ABC transporters, ABCA1, ABCG1, sprouting angiogenesis, zebrafish, non-cell-autonomous regulation, vascular development
MeSH terms
Animals, Biological Transport, Blood Vessels, Carrier Proteins, Cholesterol, DNA-Binding Proteins, Embryo, Nonmammalian, Humans, Lipoproteins, HDL, Membrane Lipids, Zebrafish, Signal Transduction, ATP-Binding Cassette Transporters, Neovascularization, Physiologic, Membrane Microdomains, Zebrafish Proteins, Vascular Endothelial Growth Factor Receptor-2, Endothelial Cells, Protein Multimerization, Human Umbilical Vein Endothelial Cells

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