Evidence map›Paper›PMID 28912068›Full record

ArticleBiochemical pharmacology2017

Angiogenic imbalance and diminished matrix metalloproteinase-2 and -9 underlie regional decreases in uteroplacental vascularization and feto-placental growth in hypertensive pregnancy.

Carlos A Dias-Junior, Juanjuan Chen, Ning Cui, Charles L Chiang, Minglin Zhu, Zongli Ren, Jose S Possomato-Vieira, Raouf A Khalil

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochemical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 16% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
  2. Endothelial Dysfunction in Preeclampsia: Focus on the Uteroplacental Circulation.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Adaptive structural and functional evolution of the placenta protects fetal growth in high-elevation deer mice.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
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

8 authors at 2 institutions in 1 country.

Carlos A Dias-JuniorVascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States.
Juanjuan ChenVascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States.
Ning CuiVascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States.
Charles L ChiangVascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States.
Minglin ZhuVascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States.
Zongli RenVascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States.
Jose S Possomato-VieiraVascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States.
Raouf A KhalilVascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States. Electronic address: raouf_khalil@hms.harvard.edu.
Harvard University · USBrigham 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
NHLBI NIH HHS R01 HL065998NHLBI NIH HHS R21 HL098724NHLBI NIH HHS R21 HL111775
6 · The paper itself

Abstract

Preeclampsia is a form of hypertension-in-pregnancy (HTN-Preg) with unclear mechanism. Generalized reduction of uterine perfusion pressure (RUPP) could be an initiating event leading to uteroplacental ischemia, angiogenic imbalance, and HTN-Preg. Additional regional differences in uteroplacental blood flow could further affect the pregnancy outcome and increase the risk of preeclampsia in twin or multiple pregnancy, but the mechanisms involved are unclear. To test the hypothesis that regional differences in angiogenic balance and matrix metalloproteinases (MMPs) underlie regional uteroplacental vascularization and feto-placental development, we compared fetal and placental growth, and placental and myoendometrial vascularization in the proximal, middle and distal regions of the uterus (in relation to the iliac bifurcation) in normal pregnant (Preg) and RUPP rats. Maternal blood pressure and plasma anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1)/placenta growth factor (PIGF) ratio were higher, and average placentae number, placenta weight, litter size, and pup weight were less in RUPP than Preg rats. The placenta and pup number and weight were reduced, while the number and diameter of placental and adjacent myoendometrial arteries, and MMP-2 and MMP-9 levels/activity were increased, and sFlt-1/PlGF ratio was decreased in distal vs proximal uterus of Preg rats. In RUPP rats, the placenta and pup number and weight, the number and diameter of placental and myoendometrial arteries, and MMP-2 and -9 levels/activity were decreased, and sFlt-1/PlGF ratio was increased in distal vs proximal uterus. Treatment with sFlt-1 or RUPP placenta extract decreased MMP-2 and MMP-9 in distal segments of Preg uterus, and treatment with PIGF or Preg placenta extract restored MMP levels in distal segments of RUPP uterus. Thus, in addition to the general reduction in placental and fetal growth during uteroplacental ischemia, localized angiogenic imbalance and diminished MMP-2 and MMP-9 could cause further decrease in placental and myoendometrial vascularization and placental and fetal growth in distal vs proximal uterus of HTN-Preg rats. Regional differences in uteroplacental perfusion, angiogenic balance and MMPs could be a factor in the incidence of preeclampsia in multiple pregnancy.

Indexed as

AnimalsFemaleFetal DevelopmentGene Expression Regulation, EnzymologicHypertensionMatrix Metalloproteinase 2Matrix Metalloproteinase 9Neovascularization, PhysiologicPlacentaPlacental CirculationPregnancyPregnancy ComplicationsRatsRats, Sprague-DawleyUterusVascular Endothelial Growth Factor Receptor-1Flt1 protein, ratMatrix Metalloproteinase 2Matrix Metalloproteinase 9Vascular Endothelial Growth Factor Receptor-1AngiogenesisHypertensionMatrix metalloproteinasesMultiple pregnancyPreeclampsia

Identifiers

PMID28912068
PMCPMC5705464
OpenAlexW2754382115

What OpenQuestion holds

Textmetadata
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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.