cis-9,trans-11 conjugated linoleic acid stimulates expression of angiopoietin like-4 in the placental extravillous trophoblast cells.
A number of studies have been carried out to examine the biological function of conjugated linoleic acid (CLA) and its potential health benefits. However, not much is known about how CLA isomers mediate their effect on angiogenesis and vascularization during early placentation. In this paper we demonstrate that cis-9,trans-11(c9,t11)-CLA stimulated the expression of angiopoietin like-4 (ANGPTL4) mRNA and protein accompanied by tube formation in first trimester placental trophoblast cells, HTR8/SVneo whereas the other CLA isomer, trans-10,cis-12 (t10,c12)-CLA had no such effects. c9,t11-CLA however did not stimulate expression of the most potent angiogenic factor, vascular endothelial growth factor (VEGF) in these cells. Silencing ANGPTL4 in these cells significantly reduced the stimulatory effect of c9,t11-CLA on tube formation, indicating the involvement of ANGPTL4. In addition, c9,t11-CLA increased the mRNA expression of several pro-angiogenic factors such as fatty acid binding protein-4 (FABP4), cyclooxygenase-2 (COX-2) and adipose differentiation-related protein (ADRP) in HTR8/SVneo cells. c9,t11-CLA also induced the uptake of docosahexaenoic acid, 22:6n-3 (DHA), a stimulator of tube formation in these cells. Triacsin C, an acylCoA synthetase inhibitor, attenuated c9,t11-CLA induced DHA uptake, tube formation and cellular proliferation in HTR8/SVneo cells. Our data suggest that the c9,t11-CLA isomer may regulate angiogenic processes during early placentation via increased expression of ANGPTL4 and other pro-angiogenic factors such as FABP4, COX-2 and ADRP with concomitant increase in the uptake of DHA in these cells.
Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway.
Sanjay
S
Basak
Asim K
AK
Duttaroy
D042682:Angiopoietins / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics; D000070780:Perilipin-2; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D014327:Trophoblasts / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D042682:Angiopoietins; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D044243:Linoleic Acids, Conjugated; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D000070780:Perilipin-2; D042461:Vascular Endothelial Growth Factor A; C118117:angiopoietin 4; C046938:9,11-linoleic acid; D051546:Cyclooxygenase 2