Candesartan Does Not Activate PPARγ and Its Target Genes in Early Gestation Trophoblasts.
PPARγ
angiotensin II
candesartan
first-trimester pregnancy
placenta
rosiglitazone
teratogenic
trophoblast
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
14 Oct 2022
14 Oct 2022
Historique:
received:
31
08
2022
revised:
08
10
2022
accepted:
10
10
2022
entrez:
27
10
2022
pubmed:
28
10
2022
medline:
29
10
2022
Statut:
epublish
Résumé
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
Identifiants
pubmed: 36293183
pii: ijms232012326
doi: 10.3390/ijms232012326
pmc: PMC9603971
pii:
doi:
Substances chimiques
PPAR gamma
0
candesartan
S8Q36MD2XX
Rosiglitazone
05V02F2KDG
Angiotensin II
11128-99-7
Receptor, Angiotensin, Type 1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Austrian Science Fund FWF
ID : DOC 31
Pays : Austria
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