title: Docosahexaenoic acid stimulates tube formation in first trimester trophoblast cells, HTR8/SVneo.
abstract: Angiogenesis is a key factor in the placentation process and vascular remodeling that involves several growth factors such as vascular endothelial growth factor (VEGF) and angiopoietin-like protein 4 (ANGPTL4). PPARs are involved in the placentation process but not much information is available on whether their ligands such as fatty acids have any effects on these processes. We therefore investigated the effect of fatty acids (arachidonic acid, 20:4 n-6(ARA), eicosapentaenoic acid, 20:5 n-3(EPA), docosahexaenoic acid, 22:6 n-3 (DHA) and oleic acid, 18:1 n-9 (OA)) on tube formation (as a measure of angiogenesis) on matrigel in the first trimester trophoblast cells, HTR8/SVneo. In addition we also investigated the effects of fatty acids on expression of genes involved in angiogenesis (VEGF and ANGPTL4) and lipid metabolism in these cells. Gene expression was determined after incubating these cells with different fatty acids for 24 h using real-time qRT-PCR, whereas VEGF and ANGPTL4 proteins were measured by respective ELISA kits. Of all the fatty acids tested, DHA increased tube formation to the greatest extent. DHA-induced increase in tube length was 583%, 247% and 70% over control, OA and EPA, respectively (p < 0.05). In addition, DHA stimulated cell proliferation by 150% of these cells. Of all fatty acids investigated, only DHA stimulated VEGF mRNA expression and protein secretion compared with control. Unlike DHA, other fatty acids (OA, EPA, ARA) stimulated ANGPTL4 mRNA expression and protein secretion in these cells. An inhibitor of VEGF decreased DHA stimulated tube formation in these cells. Altogether these data indicate that DHA may potently influence the placentation process by stimulating tube formation and this effect may be mediated in part via VEGF in first trimester trophoblast cells.
authors: Department of Nutrition, Institute for Basic Medical Sciences, Faculty of Medicine, University of Oslo, POB 1046 Blindern, N-0316 Oslo, Norway.
authors: G M
authors: GM
authors: Johnsen
authors: Department of Nutrition, Institute for Basic Medical Sciences, Faculty of Medicine, University of Oslo, POB 1046 Blindern, N-0316 Oslo, Norway.
authors: S
authors: S
authors: Basak
authors: Department of Nutrition, Institute for Basic Medical Sciences, Faculty of Medicine, University of Oslo, POB 1046 Blindern, N-0316 Oslo, Norway.
authors: M S
authors: MS
authors: Weedon-Fekjær
authors: Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Obstetrics and Gynaecology, Oslo University Hospital, Ullevål, Oslo, Norway.
authors: A C
authors: AC
authors: Staff
authors: Department of Nutrition, Institute for Basic Medical Sciences, Faculty of Medicine, University of Oslo, POB 1046 Blindern, N-0316 Oslo, Norway. Electronic address: a.k.duttaroy@medisin.uio.no.
authors: A K
authors: AK
authors: Duttaroy
mesh_terms: D016718:Arachidonic Acid; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D005260:Female; D006801:Humans; D007797:Laminin; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019301:Oleic Acid / Q000494:pharmacology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011509:Proteoglycans; D014327:Trophoblasts / Q000187:drug effects / Q000502:physiology*
chemical_list: D004338:Drug Combinations; D005227:Fatty Acids; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019301:Oleic Acid; D003094:Collagen; D015118:Eicosapentaenoic Acid