Evidence map›Paper›PMID 24704473›Full record

ArticleBiochemical pharmacology2014

Altered matrix metalloproteinase-2 and -9 expression/activity links placental ischemia and anti-angiogenic sFlt-1 to uteroplacental and vascular remodeling and collagen deposition in hypertensive pregnancy.

Wei Li, Karina M Mata, Marc Q Mazzuca, Raouf A Khalil

Abstract read
In one paragraph

Article in Biochemical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
8.1field-weighted citation impact, top 2% 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

55 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
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  5. Review
  6. Article
  7. Beyond classical collagen: basement membrane collagen IV in age-associated lung diseases.European respiratory review : an official journal of the European Respiratory Society · 2025
    Review
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  14. [Characteristics of the left heart structure and function in 86 term neonates with intrauterine growth restriction].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023
    Article
  15. Article
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  18. Increased CaBiochemical pharmacology · 2023
    Article
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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

4 authors at 1 institution in 1 country.

Wei LiVascular Surgery Research Laboratory, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States.
Karina M MataVascular Surgery Research Laboratory, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States.
Marc Q MazzucaVascular Surgery Research Laboratory, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States.
Raouf A KhalilVascular Surgery Research Laboratory, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States. Electronic address: raouf_khalil@hms.harvard.edu.
Harvard University · 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 complication of pregnancy manifested as maternal hypertension and often fetal growth restriction. Placental ischemia could be an initiating event, but the linking mechanisms leading to hypertension and growth restriction are unclear. We have shown an upregulation of matrix metalloproteinases (MMPs) during normal pregnancy (Norm-Preg). To test the role of MMPs in hypertensive-pregnancy (HTN-Preg), maternal and fetal parameters, MMPs expression, activity and distribution, and collagen and elastin content were measured in uterus, placenta and aorta of Norm-Preg rats and in rat model of reduced uteroplacental perfusion pressure (RUPP). Maternal blood pressure was higher, and uterine, placental and aortic weight, and the litter size and pup weight were less in RUPP than Norm-Preg rats. Western blots and gelatin zymography revealed decreases in amount and gelatinase activity of MMP-2 and MMP-9 in uterus, placenta and aorta of RUPP compared with Norm-Preg rats. Immunohistochemistry confirmed reduced MMPs in uterus, placenta and aortic media of RUPP rats. Collagen, but not elastin, was more abundant in uterus, placenta and aorta of RUPP than Norm-Preg rats. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) decreased MMPs in uterus, placenta and aorta of Norm-Preg rats, and vascular endothelial growth factor (VEGF) reversed the decreases in MMPs in tissues of RUPP rats. Thus placental ischemia and anti-angiogenic sFlt-1 decrease uterine, placental and vascular MMP-2 and MMP-9, leading to increased uteroplacental and vascular collagen, and growth-restrictive remodeling in HTN-Preg. Angiogenic factors and MMP activators may reverse the decrease in MMPs and enhance growth-permissive remodeling in preeclampsia.

Indexed as

AnimalsBlood PressureCollagenFemaleGene Expression RegulationGene Expression Regulation, EnzymologicHypertensionMatrix Metalloproteinase 2Matrix Metalloproteinase 9Neovascularization, PhysiologicPlacentaPregnancyRatsRats, Sprague-DawleyUterusVascular Endothelial Growth Factor Receptor-1CollagenFlt1 protein, ratMatrix Metalloproteinase 2Matrix Metalloproteinase 9Vascular Endothelial Growth Factor Receptor-1Blood vesselsMyometriumPlacentaPreeclampsia

Identifiers

PMID24704473
PMCPMC4034157
OpenAlexW2070116321

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Registered trials

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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.