Department of Nutrition, Institute for Basic Medical Sciences, Faculty of Medicine, University of Oslo, POB 1046 Blindern, N-0316 Oslo, Norway.
Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Obstetrics and Gynaecology, Oslo University Hospital, Ullevål, Oslo, Norway.
Placenta. 2011 Sep;32(9):626-632. doi: 10.1016/j.placenta.2011.06.009. Epub 2011 Jul 7.
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.
血管生成是胎盘形成和血管重塑过程中的一个关键因素，涉及多种生长因子，如血管内皮生长因子（VEGF）和血管生成素样蛋白 4（ANGPTL4）。PPARs 参与胎盘形成过程，但关于其配体（如脂肪酸）是否对这些过程有任何影响的信息并不多。因此，我们研究了脂肪酸（花生四烯酸，20:4 n-6（ARA），二十碳五烯酸，20:5 n-3（EPA），二十二碳六烯酸，22:6 n-3（DHA）和油酸，18:1 n-9（OA））对早孕滋养层细胞 HTR8/SVneo 中基质胶管形成（作为血管生成的衡量标准）的影响。此外，我们还研究了脂肪酸对这些细胞中血管生成（VEGF 和 ANGPTL4）和脂质代谢相关基因表达的影响。使用实时 qRT-PCR 检测这些细胞在不同脂肪酸孵育 24 小时后基因表达情况，而 VEGF 和 ANGPTL4 蛋白则使用相应的 ELISA 试剂盒进行测量。在所测试的所有脂肪酸中，DHA 最大程度地增加了管形成。与对照相比，DHA 诱导的管长度增加分别为 583%、247%和 70%，OA 和 EPA（p<0.05）。此外，DHA 刺激这些细胞的增殖增加了 150%。在所研究的所有脂肪酸中，只有 DHA 与对照相比刺激了 VEGF mRNA 表达和蛋白分泌。与 DHA 不同，其他脂肪酸（OA、EPA、ARA）刺激这些细胞中 ANGPTL4 mRNA 表达和蛋白分泌。VEGF 的抑制剂降低了这些细胞中 DHA 刺激的管形成。总之，这些数据表明 DHA 可能通过刺激管形成强烈影响胎盘形成过程，而这种作用可能部分通过早孕滋养层细胞中的 VEGF 介导。
