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The intensity of the node color indicates the degree of up- (red) or down- (green) regulation. .. Dr. Egle Bytautiene, is supported by a research career development award This paper will be presented at the 33nd Annual Meeting, Society of. Society for Maternal-Fetal Medicine 38th Annual Meeting. The Pregnancy Meeting. Society for Maternal-Fetal Egle Bytautiene Prewit. Page S Download. *Corresponding Author: Egle Bytautiene Ten studies met the inclusion criteria for our review: 3 concerning DNA methylation and 7 .. () Up-regulated expression and aberrant DNA methylation of LEP and SH3PXD2A in pre- eclampsia.

Introduction Preeclampsia PE is the most common encountered complication of pregnancy and a public health problem and leads to maternal and neonatal mortality worldwide [ 1 ].

This complication is mostly characterized by new onset of hypertension and proteinuria after 20 weeks of gestation. In addition, the PE patients may show signs of renal malfunction, liver disease, and hematological disturbances [ 2 — 4 ]. Despite extensive studies, the basic etiology of PE is still unknown. However, it is confirmed that PE is a multifactorial disorder with a familial predisposition which indicates a genetic contribution [ 5 ].

During the pregnancy, there is a shift in immune cells response, T helper 1 Th1 to T helper 2 Th2for favorable implantation, thus inducing maternal tolerance and suppression [ 6 ].

In women with PE some of the cytokines released by these cells have been found to be elevated, which could be markers for progression of this syndrome [ 7 ].

Studies suggested that plasma levels of anti-inflammatory cytokines, including IL-4 as a critical cytokine of Th2, have decreased in PE patients [ 1112 ]. Interleukin-4 is the main cytokine of T helper 2 lymphocytes, which has a key role in regulation of humoral immune responses [ 13 ]. The production of this anti-inflammatory cytokine should increase during pregnancy.

Thus, the function of immune system alters during PE. Interleukin-4 IL-4 gene is mapped within the cytokine gene cluster on chromosome 5q This VNTR polymorphism contains three alleles: The frequency of RP1 allele is higher than RP2 alleles.

Likewise, RP3 allele is scarce that has been detected in few populations [ 16 ]. To the best of our knowledge the present study is the first report which aimed to investigate the probable association between IL-4 VNTR polymorphism and the risk of preeclampsia. Material and Methods 2. Population Study Ethical committee approval was received, and informed consent was obtained from patients and control women before beginning of the study.

Epigenetic Modifications of Preeclamptic Placenta-A Systematic Review | OMICS International

All individuals were recruited from the Department of Obstetrics and Gynecology of Ali-ebn-Abitaleb educational hospital of Zahedan University of Medical Sciences from to This case-control study included women with PE aged years and unrelated healthy controls aged years. Exclusion criteria included twin or multiple pregnancies or any evidence of previous medical disease. Women who were affected by systemic, infectious, cardiac, and renal diseases and also systemic lupus erythematosus were excluded.

According to the American Congress of Obstetricians and Gynecologists, the diagnostic criteria includes the development of hypertension, defined as a persistent systolic blood pressure BP of mm Hg or higher or a diastolic BP of 90 mm Hg or higher after 20 weeks of gestation in a previously normotensive woman.

Proteinuria is defined by the excretion of mg or more of protein in a 24 hour urine collection or this amount extrapolated from a timed collection. In the absence of proteinuria, the diagnosis of preeclampsia can be made if new onset hypertension occurs with new onset of any one of the following: Several studies have focused on DNA methylation changes seen in the placenta, a highly important factor in the success of fetal development.

DNA methylation is an epigenetic process during which methyl groups are inserted into DNA, leading to the inhibition of transcription [ 5 ]. When the fetus is exposed to dangerous environmental factors, it can respond with significant alterations towards its growth via DNA methylation.

For example, one study found that maternal smoking is associated with changes in DNA methylation of the RUNX1 gene, exerting a detrimental effect on the health of the fetus-the RUNX1 gene has been associated with childhood asthma and airway hyperresponsiveness [ 3 ]. Another form of placental epigenetics is witnessed in histone modification. Histone acetylation works to alter gene expression through post-replication chromatin assembly using specific enzymes as previously mentioned, such as HAT and HDAC.

Environmental factors also play an important role here as they promote histone acetylation changes during crucial cell cycle steps [ 6 ]. These short, non-coding RNA segments act as silencers of post-transcriptional gene expression by base pairing with, rather than degrading, mRNA.

Possible Association of IL-4 VNTR Polymorphism with Susceptibility to Preeclampsia

By targeting mRNA, they are able to upregulate or downregulate gene expression, without altering the gene itself [ 2 ]. The regulation of placental development by miRNAs has been shown through the control of trophoblast cell proliferation, migration, invasion, apoptosis, and angiogenesis [ 7 ].

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To our current knowledge, there are no existing systematic reviews of the knowledge accumulated on all epigenetic modifications in the preeclamptic placenta, including miRNA, DNA methylation and histone modification by acetylation. Here we compiled the current literature using a rigorous systematic review method that have identified the most robust of these studies in hopes of detecting both the key discoveries as well as identifying the biggest gaps in knowledge for future studies.

Search results were limited to humans, English language, last ten-year periodand non-review articles Figure 1after which articles remained.

Epigenetic Modifications of Preeclamptic Placenta-A Systematic Review

Flow of literature search. The mechanism be- uterine artery ligation, alteration of vascular function hind this improvement appears to be endothelium by impairment in the nitric oxide system by knocking dependent and involves reduction in the serum sFlt-1 out the endothelial nitric oxide synthase gene, chronic level. Most animal models lack some features of enzyme catalyzing the early rate-limiting step in cho- preeclampsia in humans, thus making extrapolation lesterol biosynthesis, the conversion of 3-hydroxy or application of our results clinically even more methyl-glutaryl-coenzyme A to mevalonate.

With the addition of L-NAME, a nonse- bypasses low-density lipoprotein cholesterol lowering lective inhibitor of nitric oxide synthase, the re- to other pleiotropic effects such as anti-inflammatory, sponses to phenylephrine in the sFltpravastatin up-regulation of endothelial nitric oxide synthase, group were still much lower compared with those of inhibition of smooth muscle cells proliferation, de- the sFlt-1 animals not treated with pravastatin, al- crease in oxygen free radical formation as well as though the difference did not reach statistical signifi- immunomodulatory effects.

Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med ; Heme oxygenase-1 is an inducible antioxidant defense protein with cytoprotective and anti-inflam- 7.

Prediction and prevention of recurrent preeclampsia. Obstet Gynecol ; 2 pt 1: The benefits of statins in people without carbon monoxide CO and iron.

Patients with pre- established cardiovascular disease but with cardiovascular risk eclampsia have significantly decreased CO concen- factors: Primary prevention of cardiovascular mortality and events with genase J Am Coll Cardiol ; The effect of over-expression of sFlt-1 on blood pressure and the occurrence of other manifestations of pre- soluble endoglin release from endothelial cells and eclampsia in unrestrained conscious pregnant mice.

Am J placental explants. J Clin Invest ; Recombinant adenovirus as a methodology for exploration of physiologic functions of point and requires more investigation and verifica- growth factor pathway. J Mol Med ; Other potential mechanisms that were not eval- Statin treatment in hypercholesterolemic preg- statin on free oxygen radical formation and cytokine nant mice reduced cardiovascular risk factors in their offspring.

A simple sequentially rejective multiple test proce- dure. Scand J Stat ;6: In conclusion, we found that pravastatin im- proved the vascular reactivity in this murine model of Clinical pharmacokinetics of pravastatin: Clin Pharmacokinet ; preeclampsia by decreasing sFlt-1 levels.

We also believe that MacFarlane PW, et al. Prevention of coronary heart disease pregnancy should be considered the window to a with Pravastatin in men with hypercholesterolemia.

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Prevention of cardiovascular events and death with pravastatin metabolic profiles need to be identified and treated in in patients with coronary heart disease and a broad range of an effort to decrease their future risk of cardiovascular initial cholesterol levels. The Long-Term Intervention with disease. Diagnosis and management of preeclampsia and eclampsia.