Control of Angiogenesis by AIBP-mediated Cholesterol Efflux

Control of Angiogenesis by AIBP-mediated Cholesterol Efflux

Cholesterol is a structural component of the cell, indispensable for normal cellular function, but 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 efflu...

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Main Authors: Fang, Longhou, Choi, Soo-Ho, Baek, Ji Sun, Liu, Chao, Almazan, Felicidad, Ulrich, Florian, Wiesner, Philipp, Taleb, Adam, Deer, Elena, Pattison, Jennifer, Torres-Vázquez, Jesús, Li, Andrew C., Miller, Yury I.
Format: Online
Language:English
Published: 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760669/
id pubmed-3760669
recordtype oai_dc
spelling pubmed-37606692013-12-06 Control of Angiogenesis by AIBP-mediated Cholesterol Efflux Fang, Longhou Choi, Soo-Ho Baek, Ji Sun Liu, Chao Almazan, Felicidad Ulrich, Florian Wiesner, Philipp Taleb, Adam Deer, Elena Pattison, Jennifer Torres-Vázquez, Jesús Li, Andrew C. Miller, Yury I. Article Cholesterol is a structural component of the cell, indispensable for normal cellular function, but 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 to the ApoA-I-containing high-density lipoprotein (HDL)1-3. Maintaining efficient cholesterol efflux is essential for normal cellular function4-6. 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 (EC) to HDL and thereby regulates angiogenesis. AIBP/HDL-mediated cholesterol depletion reduces lipid rafts, interferes with VEGFR2 dimerization and signaling, and inhibits VEGF-induced angiogenesis in vitro and mouse aortic neovascularization ex vivo. Remarkably, Aibp regulates the membrane lipid order in embryonic zebrafish vasculature and functions as a non-cell autonomous regulator of zebrafish angiogenesis. Aibp knockdown results in dysregulated sprouting/branching angiogenesis, while forced Aibp expression inhibits angiogenesis. Dysregulated angiogenesis is phenocopied in Abca1/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 EC and that effective cholesterol efflux is critical for proper angiogenesis. 2013-05-29 2013-06-06 /pmc/articles/PMC3760669/ /pubmed/23719382 http://dx.doi.org/10.1038/nature12166 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Fang, Longhou
Choi, Soo-Ho
Baek, Ji Sun
Liu, Chao
Almazan, Felicidad
Ulrich, Florian
Wiesner, Philipp
Taleb, Adam
Deer, Elena
Pattison, Jennifer
Torres-Vázquez, Jesús
Li, Andrew C.
Miller, Yury I.
spellingShingle Fang, Longhou
Choi, Soo-Ho
Baek, Ji Sun
Liu, Chao
Almazan, Felicidad
Ulrich, Florian
Wiesner, Philipp
Taleb, Adam
Deer, Elena
Pattison, Jennifer
Torres-Vázquez, Jesús
Li, Andrew C.
Miller, Yury I.
Control of Angiogenesis by AIBP-mediated Cholesterol Efflux
author_facet Fang, Longhou
Choi, Soo-Ho
Baek, Ji Sun
Liu, Chao
Almazan, Felicidad
Ulrich, Florian
Wiesner, Philipp
Taleb, Adam
Deer, Elena
Pattison, Jennifer
Torres-Vázquez, Jesús
Li, Andrew C.
Miller, Yury I.
author_sort Fang, Longhou
title Control of Angiogenesis by AIBP-mediated Cholesterol Efflux
title_short Control of Angiogenesis by AIBP-mediated Cholesterol Efflux
title_full Control of Angiogenesis by AIBP-mediated Cholesterol Efflux
title_fullStr Control of Angiogenesis by AIBP-mediated Cholesterol Efflux
title_full_unstemmed Control of Angiogenesis by AIBP-mediated Cholesterol Efflux
title_sort control of angiogenesis by aibp-mediated cholesterol efflux
description Cholesterol is a structural component of the cell, indispensable for normal cellular function, but 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 to the ApoA-I-containing high-density lipoprotein (HDL)1-3. Maintaining efficient cholesterol efflux is essential for normal cellular function4-6. 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 (EC) to HDL and thereby regulates angiogenesis. AIBP/HDL-mediated cholesterol depletion reduces lipid rafts, interferes with VEGFR2 dimerization and signaling, and inhibits VEGF-induced angiogenesis in vitro and mouse aortic neovascularization ex vivo. Remarkably, Aibp regulates the membrane lipid order in embryonic zebrafish vasculature and functions as a non-cell autonomous regulator of zebrafish angiogenesis. Aibp knockdown results in dysregulated sprouting/branching angiogenesis, while forced Aibp expression inhibits angiogenesis. Dysregulated angiogenesis is phenocopied in Abca1/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 EC and that effective cholesterol efflux is critical for proper angiogenesis.
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760669/
_version_ 1612007920633905152

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