ApoB-containing lipoproteins regulate angiogenesis by modulating expression of VEGF receptor 1

被引：107

作者：

Avraham-Davidi, Inbal ^{[1
]}

Ely, Yona ^{[1
]}

Pham, Van N. ^{[2
]}

Castranova, Daniel ^{[2
]}

Grunspan, Moshe ^{[1
]}

Malkinson, Guy ^{[1
]}

Gibbs-Bar, Liron ^{[1
]}

Mayseless, Oded ^{[1
]}

Allmog, Gabriella ^{[1
]}

Lo, Brigid ^{[2
]}

Warren, Carmen M. ^{[3
]}

Chen, Tom T. ^{[3
]}

Ungos, Josette ^{[2
]}

Kidd, Kameha ^{[2
]}

Shaw, Kenna ^{[2
]}

Rogachev, Ilana ^{[4
]}

Wan, Wuzhou ^{[5
]}

Murphy, Philip M. ^{[5
]}

Farber, Steven A. ^{[6
]}

Carmel, Liran ^{[7
]}

Shelness, Gregory S. ^{[8
]}

Iruela-Arispe, M. Luisa ^{[3
]}

Weinstein, Brant M. ^{[2
]}

Yaniv, Karina ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel

[2] NICHHD, Mol Genet Lab, US Natl Inst Hlth NIH, Bethesda, MD USA

[3] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA USA

[4] Weizmann Inst Sci, Dept Plant Sci, IL-76100 Rehovot, Israel

[5] NIAID, Lab Mol Immunol, NIH, Bethesda, MD USA

[6] Carnegie Inst Sci, Dept Embryol, Baltimore, MD USA

[7] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Genet, Jerusalem, Israel

[8] Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27103 USA

来源：

NATURE MEDICINE | 2012年 / 18卷 / 06期

基金：

美国国家卫生研究院; 以色列科学基金会;

关键词：

TRIGLYCERIDE TRANSFER PROTEIN; ENDOTHELIAL-CELLS; APOLIPOPROTEIN-B; ZEBRAFISH; HYPERCHOLESTEROLEMIA; ABETALIPOPROTEINEMIA; METABOLISM; VERTEBRATE; PLASMA; GENES;

D O I：

10.1038/nm.2759

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Despite the clear major contribution of hyperlipidemia to the prevalence of cardiovascular disease in the developed world, the direct effects of lipoproteins on endothelial cells have remained obscure and are under debate. Here we report a previously uncharacterized mechanism of vessel growth modulation by lipoprotein availability. Using a genetic screen for vascular defects in zebrafish, we initially identified a mutation, stalactite (stl), in the gene encoding microsomal triglyceride transfer protein (mtp), which is involved in the biosynthesis of apolipoprotein B (ApoB)-containing lipoproteins. By manipulating lipoprotein concentrations in zebrafish, we found that ApoB negatively regulates angiogenesis and that it is the ApoB protein particle, rather than lipid moieties within ApoB-containing lipoproteins, that is primarily responsible for this effect. Mechanistically, we identified downregulation of vascular endothelial growth factor receptor 1 (VEGFR1), which acts as a decoy receptor for VEGF, as a key mediator of the endothelial response to lipoproteins, and we observed VEGFR1 downregulation in hyperlipidemic mice. These findings may open new avenues for the treatment of lipoprotein-related vascular disorders.

引用

页码：967 / +

页数：10

共 53 条

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The T box transcription factor no tail in ciliated cells controls zebrafish left-right asymmetry [J].