Evidence map›Paper›PMID 25916268›Full record

ReviewBiochemical pharmacology2015

Bioactive factors in uteroplacental and systemic circulation link placental ischemia to generalized vascular dysfunction in hypertensive pregnancy and preeclampsia.

Dania A Shah, Raouf A Khalil

Abstract readReview
In one paragraph

Review in Biochemical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 2 pooled it
13.4field-weighted citation impact, top 1% 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

93 citing papers in PubMed, 2 syntheses or guidelines pooled it, 424 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Review
  6. Article
  7. Review
  8. The Role of Angiogenetic Factors in Preeclampsia.International journal of molecular sciences · 2025
    Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. A Review of the Diagnosis, Risk Factors, and Role of Angiogenetic Factors in Hypertensive Disorders of Pregnancy.Medical science monitor : international medical journal of experimental and clinical research · 2025
    Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. A Novel Stem Cell Model to Study Preeclampsia Endothelial Dysfunction.Reproductive sciences (Thousand Oaks, Calif.) · 2024
    Article

33 more citing papers are in PubMed but not listed here.

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

2 authors at 1 institution in 1 country.

Dania A ShahVascular Surgery Research Laboratory, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Raouf A KhalilVascular Surgery Research Laboratory, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA. Electronic address: raouf_khalil@hms.harvard.edu.
Brigham and Women's Hospital · US

Funding

Vascular Mechanisms in Pregnancy-Induced HypertensionR01HL065998 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI KHALIL, RAOUF A · 2002 to 2016
$4.3M
Role of Endothelin B Receptor in Vascular Protection in FemalesR21HL098724 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI KHALIL, RAOUF A · 2010 to 2011
$481k
Mechano-Sensitive Hypoxia-Inducible Factor-MMP Pathway in Venous InsufficiencyR21HL111775 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI KHALIL, RAOUF A · 2013 to 2014
$475k
Vascular Angiotensin Type-2 Receptor in Normal and Hypertensive PregnancyR03HD060702 · NICHD · BRIGHAM AND WOMEN'S HOSPITAL · PI KHALIL, RAOUF A · 2009 to 2010
$172k
NHLBI NIH HHS HL-111775NHLBI NIH HHS HL-65998NHLBI NIH HHS HL-98724NHLBI NIH HHS R01 HL065998NHLBI NIH HHS R21 HL098724NHLBI NIH HHS R21 HL111775NICHD NIH HHS HD-60702NICHD NIH HHS R03 HD060702
6 · The paper itself

Abstract

Preeclampsia is a pregnancy-associated disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality; however, the pathophysiological mechanisms involved are unclear. Predisposing demographic, genetic and environmental risk factors could cause localized abnormalities in uteroplacental cytoactive factors such as integrins, matrix metalloproteinases, cytokines and major histocompatibility complex molecules leading to decreased vascular remodeling, uteroplacental vasoconstriction, trophoblast cells apoptosis, and abnormal development of the placenta. Defective placentation and decreased trophoblast invasion of the myometrium cause reduction in uteroplacental perfusion pressure (RUPP) and placental ischemia/hypoxia, an important event in preeclampsia. RUPP could stimulate the release of circulating bioactive factors such as the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin that cause imbalance with the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or cause the release of inflammatory cytokines, reactive oxygen species, hypoxia-induced factor-1 and AT1 angiotensin receptor agonistic autoantibodies. The circulating bioactive factors target endothelial cells causing generalized endotheliosis, endothelial dysfunction, decreased vasodilators such as nitric oxide and prostacyclin and increased vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction. The bioactive factors also stimulate the mechanisms of VSM contraction including Ca(2+), protein kinase C, and Rho-kinase and induce extracellular matrix remodeling leading to further vasoconstriction and hypertension. While therapeutic options are currently limited, understanding the underlying mechanisms could help design new interventions for management of preeclampsia.

Indexed as

Blood CirculationAngiogenic ProteinsAnimalsBiological FactorsCytokinesEndothelium, VascularFemaleHumansHypertension, Pregnancy-InducedHypoxiaIntegrinsIschemiaMatrix MetalloproteinasesPlacentaPlacental CirculationPre-EclampsiaAngiogenic ProteinsBiological FactorsCytokinesIntegrinsMatrix MetalloproteinasesReactive Oxygen SpeciesEndotheliumExtracellular matrixHypertensionPreeclampsiaPregnancyVascular smooth muscle

Identifiers

PMID25916268
PMCPMC4449835
OpenAlexW1967661660

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.