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| Item Type: | Article |
|---|---|
| Title: | Candesartan does not activate PPAR(γ) and its target genes in early gestation trophoblasts |
| Creators Name: | Neuper, L. and Kummer, D. and Forstner, D. and Guettler, J. and Ghaffari-Tabrizi-Wizsy, N. and Fischer, C. and Juch, H. and Nonn, O. and Gauster, M. |
| Abstract: | Angiotensin II receptor 1 blockers are commonly used to treat hypertension in women of childbearing age. While the fetotoxic effects of these drugs in the second and third trimesters of pregnancy are well documented, their possible impacts on placenta development in early gestation are unknown. Candesartan, a member of this group, also acts as a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, a key regulator shown to be important for placental development. We have previously shown that trophoblasts do not express the candesartan target-receptor angiotensin II type 1 receptor AGTR1. This study investigated the possible role of candesartan on trophoblastic PPARγ and its hallmark target genes in early gestation. Candesartan did not affect the PPARγ protein expression or nuclear translocation of PPARγ. To mimic extravillous trophoblasts (EVTs) and cytotrophoblast/syncytiotrophoblast (CTB/SCT) responses to candesartan, we used trophoblast cell models BeWo (for CTB/SCT) and SGHPL-4 (EVT) cells as well as placental explants. In vitro, the RT-qPCR analysis showed no effect of candesartan treatment on PPARγ target genes in BeWo or SGHPL-4 cells. Treatment with positive control rosiglitazone, another PPARγ agonist, led to decreased expressions of (LEP) and (PPARG1) in BeWo cells and an increased expression of PPARG1 in SGHPL-4 cells. Our previous data showed early gestation-placental AGTR1 expression in fetal myofibroblasts only. In a CAM assay, AGTR1 was stimulated with angiotensin II and showed increased on-plant vessel outgrowth. These results suggest candesartan does not negatively affect PPARγ or its target genes in human trophoblasts. More likely, candesartan from maternal serum may first act on fetal-placental AGTR1 and influence angiogenesis in the placenta, warranting further research. |
| Keywords: | Candesartan, PPAR(γ), Placenta, Trophoblast, First-Trimester Pregnancy, Rosiglitazone, Teratogenic, Angiotensin II |
| Source: | International Journal of Molecular Sciences |
| ISSN: | 1422-0067 |
| Publisher: | MDPI |
| Volume: | 23 |
| Number: | 20 |
| Page Range: | 12326 |
| Date: | October 2022 |
| Official Publication: | https://doi.org/10.3390/ijms232012326 |
| PubMed: | View item in PubMed |
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