Evidence map›Paper›PMID 32854559›Full record

ArticleCirculation research2020

Shaping Waves of Bone Morphogenetic Protein Inhibition During Vascular Growth.

Pierre J Guihard, Yina Guo, Xiuju Wu, Lily Zhang, Jiayi Yao, Medet Jumabay, Yucheng Yao, Alan Garfinkel, Kristina I Boström

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

Article in Circulation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.4field-weighted citation impact, top 32% 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, 15 citations in OpenAlex.

  1. Article
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  4. Are physiological oscillations physiological?The Journal of physiology · 2026
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  10. Epigenetics enters the stage in vascular malformations.The Journal of clinical investigation · 2024
    Article
  11. 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

9 authors at 3 institutions in 3 countries.

Pierre J GuihardDivision of Cardiology, David Geffen School of Medicine at UCLA (P.J.G., Y.G., X.W., L.Z., J.Y., M.J., Y.Y., A.G., K.I.B.).
Yina GuoDivision of Cardiology, David Geffen School of Medicine at UCLA (P.J.G., Y.G., X.W., L.Z., J.Y., M.J., Y.Y., A.G., K.I.B.).
Xiuju WuDivision of Cardiology, David Geffen School of Medicine at UCLA (P.J.G., Y.G., X.W., L.Z., J.Y., M.J., Y.Y., A.G., K.I.B.).
Lily ZhangDivision of Cardiology, David Geffen School of Medicine at UCLA (P.J.G., Y.G., X.W., L.Z., J.Y., M.J., Y.Y., A.G., K.I.B.).
Jiayi YaoDivision of Cardiology, David Geffen School of Medicine at UCLA (P.J.G., Y.G., X.W., L.Z., J.Y., M.J., Y.Y., A.G., K.I.B.).
Medet JumabayDivision of Cardiology, David Geffen School of Medicine at UCLA (P.J.G., Y.G., X.W., L.Z., J.Y., M.J., Y.Y., A.G., K.I.B.).
Yucheng YaoDivision of Cardiology, David Geffen School of Medicine at UCLA (P.J.G., Y.G., X.W., L.Z., J.Y., M.J., Y.Y., A.G., K.I.B.).
Alan GarfinkelDivision of Cardiology, David Geffen School of Medicine at UCLA (P.J.G., Y.G., X.W., L.Z., J.Y., M.J., Y.Y., A.G., K.I.B.).
Kristina I BoströmDivision of Cardiology, David Geffen School of Medicine at UCLA (P.J.G., Y.G., X.W., L.Z., J.Y., M.J., Y.Y., A.G., K.I.B.).
University of Aden · YEInstitute of Molecular Medicine · INYale Cancer Center · US

Funding

ULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TONTONOZ, PETER J · 1985 to 2019
$55.2M
Molecular Mechanisms of MGP; Role in AVMsR01HL081397 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BOSTROM, KRISTINA I · 2006 to 2025
$7.7M
BMP and Notch Crosstalk in Cerebral Arteriovenous MalformationsR01NS079353 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yucheng Yao · 2012 to 2026
$5.3M
Switch of Osteogenesis in Vascular CalcificationR01HL139675 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yucheng Yao · 2018 to 2026
$3.6M
NHLBI NIH HHS P01 HL030568NHLBI NIH HHS R01 HL081397NHLBI NIH HHS R01 HL139675NINDS NIH HHS R01 NS079353
6 · The paper itself

Abstract

rationaleThe BMPs (bone morphogenetic proteins) are essential morphogens in angiogenesis and vascular development. Disruption of BMP signaling can trigger cardiovascular diseases, such as arteriovenous malformations.

objectiveA computational model predicted that BMP4 and BMP9 and their inhibitors MGP (matrix gamma-carboxyglutamic acid [Gla] protein) and CV2 (crossveinless-2) would form a regulatory system consisting of negative feedback loops with time delays and that BMP9 would trigger oscillatory expression of the 2 inhibitors. The goal was to investigate this regulatory system in endothelial differentiation and vascular growth. METHODS AND

resultsOscillations in the expression of MGP and CV2 were detected in endothelial cells in vitro, using quantitative real-time polymerase chain reaction and immunoblotting. These organized temporally downstream BMP-related activities, including expression of stalk-cell markers and cell proliferation, consistent with an integral role of BMP9 in vessel maturation. In vivo, the inhibitors were located in distinct zones in relation to the front of the expanding retinal network, as determined by immunofluorescence. Time-dependent changes of the CV2 location in the retina and the existence of an endothelial population with signs of oscillatory MGP expression in developing vasculature supported the in vitro findings. Loss of MGP or its BMP4-binding capacity disrupted the retinal vasculature, resulting in poorly formed networks, especially in the venous drainage areas, and arteriovenous malformations as determined by increased cell coverage and functional testing.

conclusionsOur results suggest a previously unknown mechanism of temporal orchestration of BMP4 and BMP9 activities that utilize the tandem actions of the extracellular antagonists MGP and CV2. Disruption of this mechanism may contribute to vascular malformations and disease.

Indexed as

Models, CardiovascularNeovascularization, PhysiologicAnimalsBlood VesselsBone Morphogenetic ProteinsCalcium-Binding ProteinsCarrier ProteinsExtracellular Matrix ProteinsHumansMatrix Gla ProteinBMPER protein, humanBone Morphogenetic ProteinsCalcium-Binding ProteinsCarrier ProteinsExtracellular Matrix ProteinsMatrix Gla Proteinarteriovenous malformationbone morphogenetic protein 4cardiovascular diseaseendothelial cellsmatrix Gla protein

Identifiers

PMID32854559
PMCPMC7987130
OpenAlexW3082254815

What Socratic 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 Socratic graph.