Angiogenic and Antiangiogenic Markers for Prediction and Risk Classification of Preeclampsia

Malshe, Amol; Sibai, Bahaeddine M

doi:10.1097/grf.0000000000000267

Cited by 15 publications

(10 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These include maternal versus placental, severe versus mild, and related versus unrelated derangement of the angiogenic/anti-angiogenic balance. [17][18][19][20][21][22]65,66 Furthermore, the relationship between PE and the other hypertensive disorders of pregnancy is complex and one disease may merge with another. [65][66][67][68] Because of changes in definitions and heterogeneity across studies, subtle differences cannot be captured in retrospective analyses ( Table 2).…”

Section: Discussionmentioning

confidence: 99%

A systematic review and meta-analysis indicates long-term risk of chronic and end-stage kidney disease after preeclampsia

Covella

Vinturache

Cabiddu³

et al. 2019

Kidney International

View full text Add to dashboard Cite

Preeclampsia is a pregnancy-related syndrome of variable severity, classically characterized by acute kidney involvement, with hypertension and/or proteinuria and reduced kidney function. Once considered a self-limited disease healed by delivery, it is now acknowledged that preeclampsia can affect cardiovascular and kidney health in the long term. The entity of risk has not been established and consequently follow-up policies have not been defined. Here we undertook a systematic review to gain better insights into the need for post-preeclampsia followup. Articles published between January 2000 and March 2018 were selected, dealing with at least 20 preeclampsia patients, with follow-up of 4 years or more (MEDLINE, Embase, and Cochrane Library). No quality selection or language restriction was performed. Of the 10,510 titles and abstracts originally considered, 21 papers were selected, providing information on 110,803 cases with and 2,680,929 controls without preeclampsia, with partial overlap between studies on the same databases. Heterogeneity was high, and a random meta-analytic model selected. The increase in risk of end stage renal disease after preeclampsia was significant (meta-analytic risk ratios (95% confidence interval) 6.35 (2.73-14.79)); the risk of albuminuria and chronic kidney disease increased but statistical significance was not reached (4.31 (0.95-19.58) and 2.03 (0.58-7.32), respectively). Translating meta-analytic risk into the number of patients who need follow-up to detect one adverse event, 310 patients with preeclampsia are needed to identify one woman with end stage renal disease or four to identify one woman with albuminuria. Heterogeneity in definitions, insufficient follow-up and incomplete recruitment may account for discrepancies. Thus, preeclampsia significantly increases the risk of end stage renal disease. However, there is lack of sufficient data to show a relationship between preeclampsia, albuminuria and chronic kidney disease, underlining the need for further prospective studies.

show abstract

Section: Discussionmentioning

confidence: 99%

A systematic review and meta-analysis indicates long-term risk of chronic and end-stage kidney disease after preeclampsia

Covella

Vinturache

Cabiddu³

et al. 2019

Kidney International

View full text Add to dashboard Cite

show abstract

“…It has been hypothesized that sVEGFR-1 is produced in preeclampsia because the placenta is ischemic or hypoxic, and sVEGFR-1 antagonizes angiogenic molecules, such as VEGF and placental growth factor (PlGF)(119, 143–150). Soluble endoglin is a cell surface co-receptor for transforming growth factor (TGF)-β1, which blocks TGF-β1–mediated activation of endothelial nitric oxide synthase (eNOS) and promotes vasorelaxation(124).…”

Section: Mechanisms By Which Metformin May Prevent Preeclampsiamentioning

confidence: 99%

“…There is excessive production of sVEGFR-1 and soluble endoglin in the uterus of preeclamptic patients(121) proportional to the severity of the disease (151–153) that causes maternal plasma concentrations of sVEGFR-1 and soluble endoglin to increase before preeclampsia is diagnosed, making them potential biomarkers for the disease(111, 120, 128, 129, 132, 133, 137, 138, 154–179). The increase of sVEGFR-1 causes a parallel decrease of maternal plasma concentrations of PIGF in preeclampsia(119, 143–150). …”

Section: Mechanisms By Which Metformin May Prevent Preeclampsiamentioning

confidence: 99%

Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity

Romero

Erez

Hüttemann

et al. 2017

American Journal of Obstetrics and Gynecology

203

132

View full text Add to dashboard Cite

Metformin is everywhere. Originally introduced in clinical practice as an anti-diabetic agent, its role as a therapeutic agent is expanding to include treatment of pre-diabetes, gestational diabetes, polycystic ovarian disease, and more recently, experimental studies, as well as observations in randomized clinical trials, suggest that metformin could have a place in the treatment or prevention of preeclampsia. This article provides a brief overview of the history of metformin in the treatment of diabetes, reviews the results of meta-analyses of metformin in gestational diabetes, and the treatment of obese non-diabetic pregnant women to prevent macrosomia. We highlight the results of a randomized clinical trial in which metformin administration in early pregnancy did not reduce the frequency of large-for-gestational-age infants (primary endpoint), but did decrease the frequency of preeclampsia (a secondary endpoint). The mechanisms by which metformin may prevent preeclampsia include a reduction in the production of anti-angiogenic factors (soluble vascular endothelial growth factor receptor-1 and soluble endoglin), and improving endothelial dysfunction, probably through an effect on the mitochondria. Another potential mechanism whereby metformin may play a role in the prevention of preeclampsia is its ability to modify cellular homeostasis and energy disposition, mediated by mTOR. Metformin has a molecular weight of 129 Dalton, and therefore, readily crosses the placenta. There is considerable evidence suggesting that this agent is safe during pregnancy. New literature on the role of metformin in the prevention of cancer, a chemotherapeutic adjuvant, and in prolonging life and protecting against aging, is briefly reviewed. Herein we discuss the mechanisms of action and potential benefits of metformin.

show abstract

“…Due to its highly heterogeneous presentation, definitive diagnosis of PE based solely on maternal signs and symptoms can be erroneous 87 , 88 . A variety of underlying conditions can serve as mechanistic drivers, confounding gene expression analysis of diverse patient populations.…”

Section: Discussionmentioning

confidence: 99%

FLT1 and transcriptome-wide polyadenylation site (PAS) analysis in preeclampsia

Ashar-Patel

Kaymaz

Rajakumar

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Maternal symptoms of preeclampsia (PE) are primarily driven by excess anti-angiogenic factors originating from the placenta. Chief among these are soluble Flt1 proteins (sFlt1s) produced from alternatively polyadenylated mRNA isoforms. Here we used polyadenylation site sequencing (PAS-Seq) of RNA from normal and PE human placentae to interrogate transcriptome-wide gene expression and alternative polyadenylation signatures associated with early-onset PE (EO-PE; symptom onset < 34 weeks) and late-onset PE (LO-PE; symptom onset > 34 weeks) cohorts. While we observed no general shift in alternative polyadenylation associated with PE, the EO-PE and LO-PE cohorts do exhibit gene expression profiles distinct from both each other and from normal placentae. The only two genes upregulated across all transcriptome-wide PE analyses to date (microarray, RNA-Seq and PAS-Seq) are NRIP1 (RIP140), a transcriptional co-regulator linked to metabolic syndromes associated with obesity, and Flt1. Consistent with sFlt1 overproduction being a significant driver of clinical symptoms, placental Flt1 mRNA levels strongly correlate with maternal blood pressure. For Flt1, just three mRNA isoforms account for > 94% of all transcripts, with increased transcription of the entire locus driving Flt1 upregulation in both EO-PE and LO-PE. These three isoforms thus represent potential targets for therapeutic RNA interference (RNAi) in both early and late presentations.

show abstract

Angiogenic and Antiangiogenic Markers for Prediction and Risk Classification of Preeclampsia

Cited by 15 publications

References 36 publications

A systematic review and meta-analysis indicates long-term risk of chronic and end-stage kidney disease after preeclampsia

A systematic review and meta-analysis indicates long-term risk of chronic and end-stage kidney disease after preeclampsia

Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity

FLT1 and transcriptome-wide polyadenylation site (PAS) analysis in preeclampsia

Contact Info

Product

Resources

About