Effects of fatty acids on angiogenic activity in the placental extravillious trophoblast cells

Fatty acids regulate angiogenesis although no such information is available in first trimester placental trophoblast cells despite the fact that angiogenesis is a critical step involving these cells in early placentation. We investigated effects of different fatty acids on angiogenesis, their uptake and metabolism and expression of lipid metabolic genes in first trimester placental trophoblast cells using HTR-8/SVneo cell line. Fatty acid uptake by these cells exhibited a saturable kinetics. Uptake of AA was consistently greater compared with that of EPA and DHA throughout the incubation period of 180 min. Use of triacsin C, an inhibitor of acyl-CoA synthetase, significantly inhibited fatty acid uptake as well as fatty acid induced cell proliferation in these cells. Angiogenic effect (as measured by tube formation) of these fatty acids was in the following order DHA>EPA>AA>OA. Angiogenic effect of these fatty acids (AA, EPA, OA) was significantly decreased in ANGPTL4 knocked down cells, indicating ANGPTL4 may be involved at least in part in fatty acid induced angiogenesis. In addition, these fatty acids altered expression of several lipid metabolic genes such as ADRP, FABP4, FABP3, and COX-2 those are involved in angiogenesis. All these data suggest that fatty acids regulate angiogenic processes in these cells via different mechanisms.