title: Tube formation in the first trimester placental trophoblast cells: Differential effects of angiogenic growth factors and fatty acids.
abstract: The study aims to investigate whether cytosolic fatty acid-binding protein-4 (FABP4) is involved in angiogenic growth factors- and fatty acid-induced tube formation in first trimester placental trophoblast cells, HTR8/SVneo. We determined the tube formation both at basal as well as stimulated levels in the absence and presence of inhibitors of FABP4 and VEGF signaling pathways. Basal level of tube formation was maximally reduced in the presence of 50 µM of FABP4 inhibitor compared with those by VEGF signaling pathway inhibitors (rapamycin, L-NAME, and p38 MAP kinase inhibitor). Whereas docosahexaenoic acid, 22:6n-3 (DHA)-, and VEGF-induced tube formation was maximally inhibited by p38 MAP kinase inhibitor (63.7 and 34.5%, respectively), however, leptin-induced tube formation was inhibited maximally by FABP4 inhibitor (50.7%). ANGPTL4 and oleic acid (OA)-induced tube formation was not blocked by any of these inhibitors. The FABP4 inhibitor inhibited cell growth stimulated by DHA, leptin, VEGF, and OA (P < 0.05) but was not affected by ANGPTL4. VEGF, leptin, and OA also increased FABP4 protein level in these cells, though the uptake of fatty acids by these cells was not affected by the presence of FABP4 inhibitor. Our data demonstrate that FABP4 may be involved in part in the basal level, and stimulated tube formation by VEGF, DHA, and leptin, whereas it has little or no effect in ANGPTL4- and OA-induced tube formation in these cells. Thus, FABP4 may play a differential role in fatty acids and angiogenic growth factors-mediated tube formation in the first trimester trophoblast cells in vitro.
authors.affiliation: Faculty of Medicine, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Abhilash D
authors.initials: AD
authors.lastname: Pandya
authors.affiliation: Faculty of Medicine, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Mrinal K
authors.initials: MK
authors.lastname: Das
authors.affiliation: Faculty of Medicine, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Arnab
authors.initials: A
authors.lastname: Sarkar
authors.affiliation: National Institute of Nutrition, Hyderabad, India.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Vilasagaram
authors.affiliation: National Institute of Nutrition, Hyderabad, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Basak
authors.affiliation: Faculty of Medicine, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Asim K
authors.initials: AK
authors.lastname: Duttaroy
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050556:Fatty Acid-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D020738:Leptin / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000502:physiology; D019301:Oleic Acid / Q000378:metabolism; D010920:Placenta / Q000098:blood supply / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism; D011261:Pregnancy Trimester, First; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C474772:ANGPTL4 protein, human; D043925:Angiogenesis Inducing Agents; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D020738:Leptin; D011257:Pregnancy Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019301:Oleic Acid
keywords: ANGPTL4; DHA; FABP4; FABP4 inhibitor; HTR8/SVneo cells; VEGF; first trimester trophoblast cells; tube formation