title: Dual role of fatty acid-binding protein 5 on endothelial cell fate: a potential link between lipid metabolism and angiogenic responses.
abstract: Fatty acid-binding proteins (FABP) are small molecular mass intracellular lipid chaperones that are expressed in a tissue-specific manner with some overlaps. FABP4 and FABP5 share ~55 % amino acid sequence homology and demonstrate synergistic effects in regulation of metabolic and inflammatory responses in adipocytes and macrophages. Recent studies have shown that FABP4 and FABP5 are also co-expressed in a subset of endothelial cells (EC). FABP4, which has a primarily microvascular distribution, enhances angiogenic responses of ECs, including proliferation, migration, and survival. However, the vascular expression of FABP5 has not been well characterized, and the role of FABP5 in regulation of angiogenic responses in ECs has not been studied to date. Herein we report that while FABP4 and FABP5 are co-expressed in microvascular ECs in several tissues, FABP5 expression is also detected in ECs of larger blood vessels. In contrast to FABP4, EC-FABP5 levels are not induced by VEGF-A or bFGF. FABP5 deficiency leads to a profound impairment in EC proliferation and chemotactic migration. These effects are recapitulated in an ex vivo assay of angiogenesis, the aortic ring assay. Interestingly, in contrast to FABP4-deficient ECs, FABP5-deficient ECs are significantly more resistant to apoptotic cell death. The effect of FABP5 on EC proliferation and survival is mediated, only in part, by PPARδ-dependent pathways. Collectively, these findings demonstrate that EC-FABP5, similar to EC-FABP4, promotes angiogenic responses under certain conditions, but it can also exert opposing effects on EC survival as compared to EC-FABP4. Thus, the balance between FABP4 and FABP5 in ECs may be important in regulation of angiogenic versus quiescent phenotypes in blood vessels.
authors.affiliation: Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.|Department of Obstetrics and Gynecology, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Chen-Wei
authors.initials: CW
authors.lastname: Yu
authors.affiliation: Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Lipsky
authors.affiliation: Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.|Department of Molecular Biology, Hacettepe University, Beytepe, Ankara, Turkey.
authors.forename: Cagatay
authors.initials: C
authors.lastname: Karaaslan
authors.affiliation: Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Harry
authors.initials: H
authors.lastname: Kozakewich
authors.affiliation: Department of Genetics and Complex Diseases and Sabri Ülker Center, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Gokhan S
authors.initials: GS
authors.lastname: Hotamisligil
authors.affiliation: Vascular Biology Program and Department of Surgery, Harvard Medical School, Boston, MA, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: Bischoff
authors.affiliation: Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. scataltepe@partners.org.
authors.forename: Sule
authors.initials: S
authors.lastname: Cataltepe
mesh_terms: D000818:Animals; D001011:Aorta / Q000502:physiology; D016923:Cell Death; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D002633:Chemotaxis; D019610:Cytoprotection; D050556:Fatty Acid-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000172:deficiency / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D047494:PPAR delta / Q000378:metabolism
chemical_list: C493412:FABP5 protein, human; C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D047494:PPAR delta
keywords: Angiogenesis; Aortic ring assay; Apoptosis; Cell survival; Endothelial cell; FABP4; FABP5; PPAR