The potential role of statins in preeclampsia and dyslipidemia during gestation: a narrative review

Maierean, Serban; Mikhailidis, Dimitri P.; Tóth, Peter P.; Grzesiak, Mariusz; Mazidi, Moshen; Maciejewski, Marek; Banach, Maciej

doi:10.1080/13543784.2018.1465927

Cited by 37 publications

(25 citation statements)

References 65 publications

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“…A large prospective study showed limited preventive effect of administration of low-dose anti-inflammatory and antiplatelet agent aspirin on preeclampsia development (57). Pravastatin, used for treatment of dyslipidemia and prevention of CVD, is a suggested candidate for treatment and prevention of preeclampsia (58). In addition to reducing hypercholesterolemia, statins may ameliorate major pathological responses involved in preeclampsia, including inhibition of sFlt-1 release and reduction of inflammation and oxidative stress (59).…”

Section: Discussionmentioning

confidence: 99%

Cholesterol Crystals and NLRP3 Mediated Inflammation in the Uterine Wall Decidua in Normal and Preeclamptic Pregnancies

et al. 2020

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Preeclampsia is a hypertensive and inflammatory pregnancy disorder associated with cholesterol accumulation and inflammation at the maternal-fetal interface. Preeclampsia can be complicated with fetal growth restriction (FGR) and shares risk factors and pathophysiological mechanisms with cardiovascular disease. Cholesterol crystal mediated NLRP3 inflammasome activation is central to cardiovascular disease and the pathway has been implicated in placental inflammation in preeclampsia. Direct maternal-fetal interaction occurs both in the uterine wall decidua and at the placental surface and these aligned sites constitute the maternal-fetal interface. This study aimed to investigate cholesterol crystal accumulation and NLRP3 inflammasome expression by maternal and fetal cells in the uterine wall decidua of normal and preeclamptic pregnancies. Pregnant women with normal ( n = 43) and preeclamptic pregnancies with ( n = 28) and without ( n = 19) FGR were included at delivery. Cholesterol crystals were imaged in decidual tissue by both second harmonic generation microscopy and polarization filter reflected light microscopy. Quantitative expression analysis of NLRP3, IL-1β and cell markers was performed by immunohistochemistry and automated image processing. Functional NLRP3 activation was assessed in cultured decidual explants. Cholesterol crystals were identified in decidual tissue, both in the tissue stroma and near uterine vessels. The cholesterol crystals in decidua varied between pregnancies in distribution and cluster size. Decidual expression of the inflammasome components NLRP3 and IL-1β was located to fetal trophoblasts and maternal leukocytes and was strongest in areas of proximity between these cell types. Pathway functionality was confirmed by cholesterol crystal activation of IL-1β in cultured decidual explants. Preeclampsia without FGR was associated with increased trophoblast dependent NLRP3 and IL-1β expression, particularly in the decidual areas of trophoblast and leukocyte proximity. Our findings suggest that decidual accumulation of cholesterol crystals may activate the NLRP3 inflammasome and contribute to decidual inflammation and that this pathway is strengthened in areas with close maternal-fetal interaction in preeclampsia without FGR.

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Section: Discussionmentioning

confidence: 99%

Cholesterol Crystals and NLRP3 Mediated Inflammation in the Uterine Wall Decidua in Normal and Preeclamptic Pregnancies

et al. 2020

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“…Statins have emerged as a possible treatment for pre-eclampsia in the general population, recently reviewed by Maierean et al . 88 It is a problem that a small percentage of all individuals are intolerant to statins, but as of now there is no convincing evidence that statins are teratogenic in humans. In a small study of 21 women with APS who developed pre-eclampsia and/or IUGR while on treatment with LMWH and LDA, the addition of pravastatin reduced complication rates.…”

Section: Management Of Oapsmentioning

confidence: 99%

Obstetric antiphospholipid syndrome

et al. 2018

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The present clinical and laboratory classification criteria for antiphospholipid syndrome (APS) were established in Sydney, Australia, in 2006. In this review, we focus on the obstetric subset of APS (OAPS), defined by persistent positivity for antiphospholipid antibodies together with either early recurrent pregnancy loss, early fetal death, stillbirth or premature birth <34 gestational weeks due to pre-eclampsia, eclampsia and placental insufficiency. It is important to diagnose these cases since most women suffering from OAPS can, when given appropriate treatment, have successful pregnancies. Furthermore, patients with OAPS may, depending on the antibody profile, be at enhanced risk of thrombotic events later in life. We present an update on the present knowledge of possible underlying pathogenesis, risk factors and risk estimations for adverse pregnancy outcomes before and during pregnancy, current treatment concepts, and long-term outcomes for women with OAPS and their children.

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“…Mice treated with statins have shown to possess elevated levels of CO production and increased levels of plasma antioxidants, which are abrogated by HO inhibitors, indicating that the HO/CO pathway may mediate the vasodilatory actions of statins [434]. Statins do not seem to be teratogenic; however, the available evidence only shows limited, yet promising, efficacy in treating and preventing PE [435].…”

Section: Therapeutic Considerationsmentioning

confidence: 99%

Estrogen Receptors and Estrogen-Induced Uterine Vasodilation in Pregnancy

Bai

et al. 2020

IJMS

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Normal pregnancy is associated with dramatic increases in uterine blood flow to facilitate the bidirectional maternal–fetal exchanges of respiratory gases and to provide sole nutrient support for fetal growth and survival. The mechanism(s) underlying pregnancy-associated uterine vasodilation remain incompletely understood, but this is associated with elevated estrogens, which stimulate specific estrogen receptor (ER)-dependent vasodilator production in the uterine artery (UA). The classical ERs (ERα and ERβ) and the plasma-bound G protein-coupled ER (GPR30/GPER) are expressed in UA endothelial cells and smooth muscle cells, mediating the vasodilatory effects of estrogens through genomic and/or nongenomic pathways that are likely epigenetically modified. The activation of these three ERs by estrogens enhances the endothelial production of nitric oxide (NO), which has been shown to play a key role in uterine vasodilation during pregnancy. However, the local blockade of NO biosynthesis only partially attenuates estrogen-induced and pregnancy-associated uterine vasodilation, suggesting that mechanisms other than NO exist to mediate uterine vasodilation. In this review, we summarize the literature on the role of NO in ER-mediated mechanisms controlling estrogen-induced and pregnancy-associated uterine vasodilation and our recent work on a “new” UA vasodilator hydrogen sulfide (H2S) that has dramatically changed our view of how estrogens regulate uterine vasodilation in pregnancy.

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The potential role of statins in preeclampsia and dyslipidemia during gestation: a narrative review

Cited by 37 publications

References 65 publications

Cholesterol Crystals and NLRP3 Mediated Inflammation in the Uterine Wall Decidua in Normal and Preeclamptic Pregnancies

Cholesterol Crystals and NLRP3 Mediated Inflammation in the Uterine Wall Decidua in Normal and Preeclamptic Pregnancies

Obstetric antiphospholipid syndrome

Estrogen Receptors and Estrogen-Induced Uterine Vasodilation in Pregnancy

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