The role of statins in the prevention of preeclampsia

Smith, Devin D.; Costantine, Maged M.

doi:10.1016/j.ajog.2020.08.040

Cited by 58 publications

(59 citation statements)

References 87 publications

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“…Studies have occasionally reported beneficial effects from statin use; for example, Elahi et al [ 37 ] demonstrated that statin treatment in hypercholesterolemic pregnant mice reduced certain cardiovascular risk factors in their offspring. Statins also proved beneficial in preventing preeclampsia, thus ameliorating the risks of structural abnormalities to the fetus [ 18 , 38 ]. However, the use of statins in human pregnancy is currently not recommended, because of the potential teratogenic effects observed in animal experiments on one hand, and as a precaution owing to the lack of data supporting an indication for their use in pregnancy on the other.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Consequences of in Utero Exposure to Rosuvastatin: Alteration of Histone Methylation Patterns in Newborn Rat Brains

Dulka

Szabó

Lajkó

et al. 2021

IJMS

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Rosuvastatin (RST) is primarily used to treat high cholesterol levels. As it has potentially harmful but not well-documented effects on embryos, RST is contraindicated during pregnancy. To demonstrate whether RST could induce molecular epigenetic events in the brains of newborn rats, pregnant mothers were treated daily with oral RST from the 11th day of pregnancy for 10 days (or until delivery). On postnatal day 1, the brains of the control and RST-treated rats were removed for Western blot or immunohistochemical analyses. Several antibodies that recognize different methylation sites for H2A, H2B, H3, and H4 histones were quantified. Analyses of cell-type-specific markers in the newborn brains demonstrated that prenatal RST administration did not affect the composition and cell type ratios as compared to the controls. Prenatal RST administration did, however, induce a general, nonsignificant increase in H2AK118me1, H2BK5me1, H3, H3K9me3, H3K27me3, H3K36me2, H4, H4K20me2, and H4K20me3 levels, compared to the controls. Moreover, significant changes were detected in the number of H3K4me1 and H3K4me3 sites (134.3% ± 19.2% and 127.8% ± 8.5% of the controls, respectively), which are generally recognized as transcriptional activators. Fluorescent/confocal immunohistochemistry for cell-type-specific markers and histone methylation marks on tissue sections indicated that most of the increase at these sites belonged to neuronal cell nuclei. Thus, prenatal RST treatment induces epigenetic changes that could affect neuronal differentiation and development.

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Section: Discussionmentioning

confidence: 99%

Epigenetic Consequences of in Utero Exposure to Rosuvastatin: Alteration of Histone Methylation Patterns in Newborn Rat Brains

Dulka

Szabó

Lajkó

et al. 2021

IJMS

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“…Abnormal placentation leads to the release of soluble antiangiogenic factors in line with increased oxidative stress and inflammation [5] , these events induce systemic endothelial dysfunction, which in turn causes the clinical manifestations of PE. This mechanism is one of the generally accepted mechanisms for pathogenesis of PE [4] . Alternatively, placental mal-adaptations causes defective or inadequate placentation, apoptosis of invasive cytotrophoblasts [6] , inadequate expansive remodeling of the spiral arteries, reduced uteroplacental perfusion pressure [7] and placental ischemia that promotes the release of bioactive factors into the maternal circulation [6] .…”

Section: Introductionmentioning

confidence: 97%

“…Branched vascular network is crucial to development of the placenta through the regulation of blood vessel growth [1] and depends on secretion of multiple angiogenic factors especially the vascular endothelial growth factor, the placental growth factor, soluble fms-like tyrosine kinase-1 (s-Flt1) and soluble endoglin (sEng) [2] . Preeclampsia (PE) is a complication of pregnancy characterized by gestational hypertension, proteinuria and/or end organ disease [3] with considerable neonatal and maternal morbidities and mortalities [4] . Abnormal placentation leads to the release of soluble antiangiogenic factors in line with increased oxidative stress and inflammation [5] , these events induce systemic endothelial dysfunction, which in turn causes the clinical manifestations of PE.…”

Section: Introductionmentioning

confidence: 99%

Serum Soluble Endoglin Versus Serum Placental Growth Factor for Early Prediction of Preeclampsia

Bendary

Elgazzar

Mohamed

2021

Evidence Based Women's Health Journal

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Aim: Evaluation of the predictive ability of serum soluble endoglin (sEng) and placental growth factor (PLGF) levels estimated at the 12 th gestational week (GW) for discrimination of women liable to develop preeclampsia (PE). Materials and Methods: 102 PE women were diagnosed according to the American Society of Hypertension and categorized according to guidelines of American College of Obstetricians and Gynecologists. The severity of PE was judged by the difference between blood pressure (∆BP) measures at time of PE diagnosis and at time of enrolment. Blood samples were obtained at the 12 th GW for ELISA estimation of serum sEng and PLGF. Study outcomes included the predictive ability of these markers for development of PE and the relation between age, body mass index (BMI) and serum levels of studied biomarkers and ΔSBP and ΔDBP. Results: 29 and 73 women developed early-and late-onset PE, respectively and 18 women had severe, while 84 women had mild PE. At time of PE diagnosis, BP measures were increased significantly in PE women in comparison to enrolment measures and to control measures. Serum levels of sEng were significantly higher, while serum PLGF levels were significantly lower in PE women than in controls. Development of PE was positively correlated with serum sEng, while was negatively correlated with serum PLGF levels. Also, there was positive significant correlation between ΔBP and BMI and serum levels of sEng, and negative significant correlation with at enrolment BP and serum levels of PLGF. ROC curve analysis defined ΔSBP and ΔDBP by 33 and 10 mmHg as a cutoff point for diagnosis of PE and defined high serum sEng as the significant sensitive predictor for development of PE at both cutoff points. Conclusion: At 12 th GW, estimated levels of sEng and PLGF could discriminate pregnant women vulnerable for development of PE. Statistical analyses defined high serum sEng levels estimated at the 12 th GW as the significant early predictor for upcoming PE. Maternal obesity and old age are also related to PE severity and must be considered for prediction.

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“…Preeclampsia may lead to maternal complications such as eclampsia, intracranial bleeding, acute renal failure, pulmonary edema, HELLP syndrome, and DIC. The high fetal/neonatal mortality rate is caused by fetal growth restriction, stillbirth, and complications related to mostly iatrogenic prematurity [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…The rationale to use statin as a drug for preeclampsia is based on animal studies showing that pravastatin (3-hydroxy-3-methylglutaryl coenzyme-Areductase inhibitor) has a protective role at the uteroplacental interface and on vascular cells [18]. Pravastatin may protect endothelial cells, by inducing the expression of HO-1 and as such inhibiting cytokine mediated release of the anti-angiogenic factors sFlt-1 and sEng [4,19,20,22,[24][25][26][27]. Decreased levels of sFlt-1 and sEng may increase free PlGF and VEGF in the circulation.…”

Section: Introductionmentioning

confidence: 99%

INOVASIA Study: A Randomized Open Controlled Trial to Evaluate Prophylactic Pravastatin in the Prevention of Preeclampsia and its Effects on sFlt1/PLGF Levels in Pregnant Women at High Risk of Developing Preeclampsia

Akbar

Yosediputra

Re³

et al. 2021

Preprint

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Objectives The study aim is to evaluate the effect of pravastatin to prevent preeclampsia (PE) in pregnant women at a high risk of developing preeclampsia and the maternal and perinatal outcomes and the sFlt1/PLGF ratio in the Surabaya cohort of the INOVASIA trial. Setting This study involved 2 academic hospital (a tertiary and secondary center) in Surabaya, Indonesia. Participants Pregnant women at a high risk of developing PE were recruited and randomized into an intervention group (40) and a control group (40). The inclusion criteria consisted of pregnant women with positive clinical risk factor and abnormal uterine artery doppler examination at 10-20 weeks gestational age. Inteventions The control group received low dose aspirin (80 mg/day) and calcium (1 g/day), while the intervention group received additional pravastatin (20 mg twice daily) starting from 14-20 weeks gestation until delivery. Research blood samples were collected before the first dose of pravastatin, and just before delivery. Primary and Secondary Outcomes The primary outcome was the rate of maternal preeclampsia, secondary outcomes included maternal-perinatal outcomes and sFlt-1, PLGF, sFlt-1/PlGF ratio and sEng levels. Results The rate of preeclampsia was (non-significantly) lower in the pravastatin group compared with the control group (17.5% vs 35%). The pravastatin group also had a (non-significant) lower rate of severe preeclampsia, HELLP syndrome, acute kidney injury and severe hypertension. The rate of (iatrogenic) preterm delivery was significantly lower (p 0.048) in the pravastatin group (n=4) compared with the controls (n=12). Neonates in the pravastatin group had significantly higher birthweights, higher Apgar scores, and lower composite neonatal morbidity and NICU admission rates. All biomarkers show a significant deterioration in the control group compared with non-significant changes in the pravastatin group. Conclusions Pravastatin holds promise in the secondary prevention of preeclampsia and placenta-mediated adverse perinatal outcomes by improving the anti-angiogenic/pro-angiogenic imbalance. Trial Registration Clinical Trial Gov (ID: NCT03648970)

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The role of statins in the prevention of preeclampsia

Cited by 58 publications

References 87 publications

Epigenetic Consequences of in Utero Exposure to Rosuvastatin: Alteration of Histone Methylation Patterns in Newborn Rat Brains

Epigenetic Consequences of in Utero Exposure to Rosuvastatin: Alteration of Histone Methylation Patterns in Newborn Rat Brains

Serum Soluble Endoglin Versus Serum Placental Growth Factor for Early Prediction of Preeclampsia

INOVASIA Study: A Randomized Open Controlled Trial to Evaluate Prophylactic Pravastatin in the Prevention of Preeclampsia and its Effects on sFlt1/PLGF Levels in Pregnant Women at High Risk of Developing Preeclampsia

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