Kaartinen Lassi, Jääskeläinen Tiina, Sliz Eeva, Yazgeldi Gunaydin Gamze, Wedenoja Satu, Katayama Shintaro, Kajantie Eero, Rinne Valtteri, Heinonen Seppo, Kere Juha, Merikallio Heta, Sliz Eeva, Laivuori Hannele, Hukkanen Janne
Research Unit of Biomedicine and Internal Medicine, University of Oulu, Oulu, Finland.
Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland.
Ann Med. 2025 Dec;57(1):2495763. doi: 10.1080/07853890.2025.2495763. Epub 2025 Apr 29.
Liver X receptors (LXRs) are expressed in placenta and may be associated with pre-eclampsia (PE). Oxysterols act as agonists for LXRs. We recently proposed a new blood pressure-regulating circuit with oxysterol 4β-hydroxycholesterol (4βHC) acting as a hypotensive factor LXRs.
This study investigated the association between maternal plasma 4βHC, blood pressure (BP) indices, placental expression of LXR target genes, and patient characteristics using data from the Finnish Genetics of Pre-Eclampsia Consortium (FINNPEC) cohort. Plasma samples of 144 women with PE and 38 healthy pregnant controls as well as 44 PE and 40 control placental samples were available. In addition, genetic data from the FinnGen project was utilized to explore the associations of LXR alleles with PE and pregnancy hypertension.
There were no significant associations between 4βHC and BP or maternal and perinatal characteristics in FINNPEC cohort. However, plasma 4βHC was inversely correlated with the maternal body mass index. There were no associations with the genetic variants of LXRs with PE in FinnGen. LXR target genes APOD, SCARB1, TGM2, and LPCAT3 were expressed differently between PE and normal pregnancies in placental samples of FINNPEC.
Our results demonstrate that plasma 4βHC and genetic LXR variants do not play a major role in PE and BP regulation during pregnancy. However, key LXR target genes involved in lipid metabolism were expressed differently in normal and PE pregnancies. Further research is needed to understand the complexities of oxysterols, LXRs, and their potential contributions to placental function and pregnancy outcomes.
肝脏X受体（LXRs）在胎盘中表达，可能与子痫前期（PE）有关。氧化甾醇作为LXRs的激动剂。我们最近提出了一种新的血压调节回路，其中氧化甾醇4β-羟基胆固醇（4βHC）作为LXRs的降压因子。
本研究利用芬兰子痫前期遗传学联盟（FINNPEC）队列的数据，调查了母体血浆4βHC、血压（BP）指标、LXR靶基因的胎盘表达与患者特征之间的关联。可获得144例PE患者和38例健康孕妇对照的血浆样本，以及44例PE胎盘样本和40例对照胎盘样本。此外，利用FinnGen项目的基因数据来探索LXR等位基因与PE和妊娠高血压之间的关联。
在FINNPEC队列中，4βHC与血压或母体及围产期特征之间无显著关联。然而，血浆4βHC与母体体重指数呈负相关。在FinnGen中，LXRs的基因变异与PE无关联。在FINNPEC的胎盘样本中，PE妊娠和正常妊娠之间LXR靶基因APOD、SCARB1、TGM2和LPCAT3的表达存在差异。
我们的结果表明，血浆4βHC和LXR基因变异在妊娠期间的PE和血压调节中不起主要作用。然而，参与脂质代谢的关键LXR靶基因在正常妊娠和PE妊娠中的表达存在差异。需要进一步研究以了解氧化甾醇、LXRs的复杂性及其对胎盘功能和妊娠结局的潜在影响。
