Evidence map›Paper›PMID 29629873›Full record

ArticleJournal of the American Heart Association2017

A Maternally Sequestered, Biopolymer-Stabilized Vascular Endothelial Growth Factor (VEGF) Chimera for Treatment of Preeclampsia.

Omar C Logue, Fakhri Mahdi, Heather Chapman, Eric M George, Gene L Bidwell

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the American Heart Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.

  1. Pooled it
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  16. Maternal microvascular dysfunction during preeclamptic pregnancy.Clinical science (London, England : 1979) · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Omar C LogueDepartment of Neurology, University of Mississippi Medical Center, Jackson, MS.
Fakhri MahdiDepartment of Neurology, University of Mississippi Medical Center, Jackson, MS.
Heather ChapmanDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS.
Eric M GeorgeDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS gbidwell@umc.edu egeorge@umc.edu.
Gene L BidwellDepartment of Neurology, University of Mississippi Medical Center, Jackson, MS gbidwell@umc.edu egeorge@umc.edu.
University of Mississippi Medical Center · USJackson Memorial Hospital · US

Funding

Hypertension and Cardiorenal Research Training ProgramT32HL105324 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI Joey P. Granger · 2010 to 2026
$7.8M
A Novel Protein Delivery System for Therapy of PreeclampsiaR01HL121527 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI BIDWELL, GENE LEFLORE · 2014 to 2023
$4.1M
A Novel Therapy For PreeclampsiaR01HL137791 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI GEORGE, ERIC MATTHEW · 2017 to 2021
$1.9M
NHLBI NIH HHS R01 HL137791NHLBI NIH HHS T32 HL105324
6 · The paper itself

Abstract

backgroundPreeclampsia is a hypertensive syndrome that complicates 3% to 5% of pregnancies in the United States. Preeclampsia originates from an improperly vascularized and ischemic placenta that releases factors that drive systemic pathophysiology. One of these factors, soluble fms-like tyrosine kinase-1, is believed to sequester vascular endothelial growth factor (VEGF), leading to systemic endothelial dysfunction and hypertension. With the goal of targeting soluble fms-like tyrosine kinase-1 while simultaneously preventing fetal exposure to VEGF, we fused VEGF to elastin-like polypeptide, a biopolymer carrier that does not cross the placental barrier (ELP-VEGF). METHODS AND

resultsELP-VEGF restored in vitro endothelial cell tube formation in the presence of plasma from placental ischemic rats. Long-term administered ELP-VEGF in pregnant rats accumulated in maternal kidneys, aorta, liver, and placenta, but the protein was undetectable in the pups when administered at therapeutic doses in dams. Long-term administration of ELP-VEGF in a placental ischemia rat model achieved dose-dependent attenuation of hypertension, with blood pressure equal to sham controls at a dose of 5 mg/kg per day. ELP-VEGF infusion increased total plasma soluble fms-like tyrosine kinase-1 levels but dramatically reduced free plasma soluble fms-like tyrosine kinase-1 and induced urinary excretion of nitrate/nitrite, indicating enhanced renal nitric oxide signaling. ELP-VEGF at up to 5 mg/kg per day had no deleterious effect on maternal or fetal body weight. However, dose-dependent adverse events were observed, including ascites production and neovascular tissue encapsulation around the minipump.

conclusionsELP-VEGF has the potential to treat the preeclampsia maternal syndrome, but careful dosing and optimization of the delivery route are necessary.

Indexed as

BiopolymersPre-EclampsiaVascular Endothelial Growth Factor AAnimalsBlood PressureCells, CulturedDisease Models, AnimalFemaleHumansPlacenta Growth FactorPregnancyRatsRats, Sprague-DawleyBiopolymersPlacenta Growth FactorVascular Endothelial Growth Factor Aelastin‐like polypeptidematernally sequestered drug deliverypreeclampsia/pregnancysoluble fms‐like tyrosine kinase‐1therapyvascular endothelial growth factor

Identifiers

PMID29629873
PMCPMC5779036
OpenAlexW2771590854

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.