17-Hydroxyprogesterone caproate improves T cells and NK cells in response to placental ischemia; new mechanisms of action for an old drug

Publication date: Available online 2 December 2019Source: Pregnancy HypertensionAuthor(s): Jamil T. Elfarra, Jesse N. Cottrell, Denise C. Cornelius, Mark W. Cunningham, Jessica L. Faulkner, Tarek Ibrahim, Babbette Lamarca, Lorena M. AmaralAbstractPreeclampsia (PE) is new onset hypertension during pregnancy associated with increased uterine artery resistance (UARI) and an imbalance among CD4 + T lymphocytes and natural killer (NK) cells. We have shown an important role for 17-hydroxyprogesterone caproate (17-OHPC) to improve hypertension and fetal demise in the RUPP rat model of PE. However we have not examined a role for 17-OHPC to improve NK cells and CD4+TH2 cells as possible mechanisms for improved fetal weight and hypertension. Therefore, we hypothesized that 17-OHPC lowers NK cells while improving the T cell ratio in the RUPP rat. RUPP was surgically induced on gestational day 14 in pregnant rats. 17-OHPC (3.32 mg/kg) was administered intraperitoneal on day 15, UARI was measured on day 18. Blood pressure (MAP), blood and tissues were collected on GD 19. MAP in NP rats (n = 9) was 100 ± 2, 104 ± 6 in Sham rats (n = 8), 128 ± 2 in RUPP (n = 11) and 115 ± 3 mmHg in RUPP + 17-OHPC (n = 10), p 
Source: Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health - Category: OBGYN Source Type: research

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ConclusionThe present study suggested that inhibition of the expression of STOX1 could promote the effects of aspirin in the treatment of preeclampsia.
Source: Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health - Category: OBGYN Source Type: research
CONCLUSIONS: Taken together, our study revealed that uc.187 was negatively correlated to trophoblastic cell invasion, and over-expression of uc.187 could induce PE-like symptoms in a pregnant rat model by affecting the distribution of β-catenin in the cytoplasm and nucleus. PMID: 31950140 [PubMed - as supplied by publisher]
Source: American Journal of Hypertension - Category: Cardiology Authors: Tags: Am J Hypertens Source Type: research
Bassily et al1 describe significant risk factors in an obstetrical history with subsequent cardiovascular risk, including low birthweight, pre-eclampsia, gestational diabetes, and preterm labor. Moreover, there is the inference in the “fetal origins of adult disease” hypothesis that the pregnant mother “transmits” hypertension to her unborn child through “fetal programming” or “(epi)genomic” mechanisms.2 We believe that this “transmission” does take place through histologic evidence in the first few centimeter s of the fetal end of the umbilical cord.
Source: The American Journal of Medicine - Category: General Medicine Authors: Tags: Letter Source Type: research
In routine antenatal care, blood pressure is used as a screening tool for preeclampsia and its associated adverse outcomes. As such women with a blood pressure greater than 140/90 mmHg undergo further investigation and closer follow up, whereas those with lower blood pressures receive no additional care. In the non-pregnant setting, the American College of Cardiology now endorses lower hypertensive thresholds and it remains unclear whether these lower thresholds should also be considered in pregnancy.
Source: American Journal of Obstetrics and Gynecology - Category: OBGYN Authors: Tags: Original Research: Obstetrics Source Type: research
ConclusionDifferences in DNA methylation were found in placental tissue, umbilical cord white blood cells and HUVEC of patients with early onset preeclampsia compared to (un)complicated controls, but not in patients with late-onset preeclampsia. The genes showing the largest differential methylation encode insulin-like growth factor 2 binding protein and receptor and cadherin 13.
Source: Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health - Category: OBGYN Source Type: research
Publication date: Available online 14 January 2020Source: Pregnancy HypertensionAuthor(s): Lili Zheng, Jing Huang, Hongfang Kong, Fang Wang, Yuan Su, Hong XinAbstractBackgroundPre-eclampsia is a serious hypertension disease that occurs during pregnancy. Folic acid (FA) supplementation has been reported to reduce pre-eclampsia risk in pregnant women. Here, we aimed to assess whether treatment of high doses of FA in pregnant women with high pre-eclampsia risk could prevent the onset of pre-eclampsia.MethodsWe conducted a randomized clinical trial in 1576 women who had pre-eclampsia or eclampsia in their last pregnancy and ha...
Source: Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health - Category: OBGYN Source Type: research
ConclusionsThe in vitro trophoblast cell integration into endothelial cellular networks could be modified by altering media calcium through integrin switch away from integrins α5 and β4 and towards integrin α1 which may be required for healthy early trophoblast integration.
Source: Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health - Category: OBGYN Source Type: research
ConclusionThe sFlt-1/PlGF ratio appears to be a powerful tool for diagnosing and predicting preeclampsia. However, the data do not confirm the cut-off values described earlier, with longer pregnancy durations in this group of patients.
Source: Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health - Category: OBGYN Source Type: research
ConclusionWe feel these data are suggestive of increased on-aspirin platelet (re-)activity, as measured by the PFA-200 and the VerifyNow, in non-pregnant carriers of a FII-mutation, but not in carriers of FVL-mutation. Interestingly, this increased on-aspirin platelet (re-)activity is present in spite of low sTxB2 levels
Source: Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health - Category: OBGYN Source Type: research
Publication date: Available online 14 January 2020Source: Pregnancy HypertensionAuthor(s): Zain Awamleh, Victor K.M. HanAbstractPreeclampsia (PE) and intrauterine growth restriction (IUGR) are pregnancy complications resulting from abnormal placental development. As epigenetic regulators, microRNAs can regulate placental development and contribute to the disease pathophysiology by influencing the expression of genes involved in placental development or disease. Our previous study revealed an increase in miR-210-5p expression in placentae from patients with early-onset pregnancy complications and identified candidate gene t...
Source: Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health - Category: OBGYN Source Type: research
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