Journal
NATURE MEDICINE
Volume 18, Issue 6, Pages 967-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2759
Keywords
-
Funding
- Israel Science Foundation [748/2009]
- Marie Curie Actions-International Reintegration [FP7-PEOPLE-2009-RG 256393]
- Yeda-Sela Center
- Israel Cancer Research Foundation
- US National Institutes of Health (NIH) [RO1CA126935]
- NIH [T32HL069766, HL049373, R56DK093399, R01GM063904]
- Carnegie Institution for Science endowment
- G. Harold and Leila Y. Mathers Charitable Foundation
- National Institute of Child Health and Human Development, NIH,
- Foundation Leducq
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available