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

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

Content Provider	Springer Nature Link
Author	Elmasri, Harun Ghelfi, Elisa Yu, Chen wei Traphagen, Samantha Cernadas, Manuela Cao, Haiming Shi, Guo Ping Plutzky, Jorge Sahin, Mustafa Hotamisligil, Gokhan Cataltepe, Sule
Copyright Year	2012
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.
Starting Page	457
Ending Page	468
Page Count	12
File Format	PDF
ISSN	09696970
Journal	Angiogenesis
Volume Number	15
Issue Number	3
e-ISSN	15737209
Language	English
Publisher	Springer Netherlands
Publisher Date	2012-05-05
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Angiogenesis Endothelial cells FABP4 Rapamycin c-Kit Stem cell factor Oncology Cardiology Ophthalmology Cancer Research Cell Biology Biomedicine general
Content Type	Text
Resource Type	Article
Subject	Physiology Clinical Biochemistry Cancer Research

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