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• W2900765042 abstract "Statins induce heme oxygenase-1 (HO-1) expression in vitro and in vivo. Low HO-1 expression is associated with pregnancy complications, e.g. preeclampsia and recurrent miscarriages. Here, we investigated the effects of pravastatin on HO-1 expression, placental development, and fetal survival in mice with a partial HO-1 deficiency. At E14.5, untreated pregnant wild-type (WT, n=13–18), untreated HO-1+/− (Het, n=6–9), and Het mice treated with pravastatin (Het+Pravastatin, n=12–14) were sacrificed. Numbers of viable fetuses/resorbed concepti were recorded. Maternal livers and placentas were harvested for HO activity. Hematoxylin and eosin (H&E) and CD31 immunohistochemical staining were performed on whole placentas. Compared with WT, HO activity in Het livers (65±18%, P<0.001) and placentas (74±7%, P<0.001) were significantly decreased. Number of viable fetuses per dam was significantly lower in Untreated Het dams (6.0±2.2) compared with WT (9.1±1.4, P<0.01), accompanied by a higher relative risk (RR) for concepti resorption (17.1, 95% CI 4.0–73.2). In Hets treated with pravastatin, maternal liver and placental HO activity increased, approaching levels of WT controls (to 83±7% and 87±14%, respectively). The number of viable fetuses per dam increased to 7.7±2.5 with a decreased RR for concepti resorption (2.7, 95% CI 1.2–5.9). In some surviving Untreated Het placentas, there were focal losses of cellular architecture and changes suggestive of reduced blood flow in the labyrinth. These findings were absent in Het+Pravastatin placentas. Pravastatin induces maternal liver and placental HO activity, may affect placental function and improve fetal survival in the context of a partial deficiency of HO-1." @default.
• W2900765042 created "2018-11-29" @default.
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• W2900765042 date "2019-01-01" @default.
• W2900765042 modified "2023-10-16" @default.
• W2900765042 title "Pravastatin improves fetal survival in mice with a partial deficiency of heme oxygenase-1" @default.
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• W2900765042 doi "https://doi.org/10.1016/j.placenta.2018.11.001" @default.
• W2900765042 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30712660" @default.
• W2900765042 hasPublicationYear "2019" @default.
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