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Angiogenesis
Published in: Angiogenesis 3/2012

01-09-2012 | Original Paper

Endothelial cell-fatty acid binding protein 4 promotes angiogenesis: role of stem cell factor/c-kit pathway

Authors: Harun Elmasri, Elisa Ghelfi, Chen-wei Yu, Samantha Traphagen, Manuela Cernadas, Haiming Cao, Guo-Ping Shi, Jorge Plutzky, Mustafa Sahin, Gokhan Hotamisligil, Sule Cataltepe

Published in: Angiogenesis | Issue 3/2012

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Abstract

Fatty acid binding protein 4 (FABP4) plays an important role in regulation of glucose and lipid homeostasis as well as inflammation through its actions in adipocytes and macrophages. FABP4 is also expressed in a subset of endothelial cells, but its role in this cell type is not known. We found that FABP4-deficient human umbilical vein endothelial cells (HUVECs) demonstrate a markedly increased susceptibility to apoptosis as well as decreased migration and capillary network formation. Aortic rings from FABP4−/− mice demonstrated decreased angiogenic sprouting, which was recovered by reconstitution of FABP4. FABP4 was strongly regulated by mTORC1 and inhibited by Rapamycin. FABP4 modulated activation of several important signaling pathways in HUVECs, including downregulation of P38, eNOS, and stem cell factor (SCF)/c-kit signaling. Of these, the SCF/c-kit pathway was found to have a major role in attenuated angiogenic activity of FABP4-deficient ECs as provision of exogenous SCF resulted in a significant recovery in cell proliferation, survival, morphogenesis, and aortic ring sprouting. These data unravel a novel pro-angiogenic role for endothelial cell-FABP4 and suggest that it could be exploited as a potential target for diseases associated with pathological angiogenesis.
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Metadata
Title
Endothelial cell-fatty acid binding protein 4 promotes angiogenesis: role of stem cell factor/c-kit pathway
Authors
Harun Elmasri
Elisa Ghelfi
Chen-wei Yu
Samantha Traphagen
Manuela Cernadas
Haiming Cao
Guo-Ping Shi
Jorge Plutzky
Mustafa Sahin
Gokhan Hotamisligil
Sule Cataltepe
Publication date
01-09-2012
Publisher
Springer Netherlands
Published in
Angiogenesis / Issue 3/2012
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-012-9274-0

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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