Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Neuper, L; Kummer, D; Forstner, D; Guettler, J; Ghaffari-Tabrizi-Wizsy, N; Fischer, C; Juch, H; Nonn, O; Gauster, M.
Candesartan Does Not Activate PPARγ and Its Target Genes in Early Gestation Trophoblasts.
Int J Mol Sci. 2022; 23(20):
Doi: 10.3390/ijms232012326
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- Führende Autor*innen der Med Uni Graz
- Neuper Lena
- Nonn Olivia
- Co-Autor*innen der Med Uni Graz
- Forstner Desiree
- Gauster Martin
- Ghaffari Tabrizi-Wizsy Nassim
- Güttler Jacqueline
- Juch Herbert
- Kummer Daniel
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Female - administration & dosage
- Pregnancy - administration & dosage
- Humans - administration & dosage
- Trophoblasts - metabolism
- PPAR gamma - genetics, metabolism
- Placenta - metabolism
- Rosiglitazone - pharmacology
- Angiotensin II - metabolism
- Receptor, Angiotensin, Type 1 - genetics, metabolism
- Placentation - administration & dosage
- Find related publications in this database (Keywords)
- candesartan
- PPAR gamma
- placenta
- trophoblast
- first-trimester pregnancy
- rosiglitazone
- teratogenic
- angiotensin II