Evidence map›Paper›PMID 25863249›Full record

ArticleCell metabolism2015

BMPR2 preserves mitochondrial function and DNA during reoxygenation to promote endothelial cell survival and reverse pulmonary hypertension.

Isabel Diebold, Jan K Hennigs, Kazuya Miyagawa, Caiyun G Li, Nils P Nickel, Mark Kaschwich, Aiqin Cao, Lingli Wang, Sushma Reddy, Pin-I Chen and 6 more

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

Article in Cell metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed
13.2field-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

146 citing papers in PubMed, 214 citations in OpenAlex.

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  12. Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025
    Review
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  19. Review
  20. Article

86 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

16 authors at 2 institutions in 1 country.

Isabel DieboldDepartment of Pediatrics and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; The Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jan K HennigsDepartment of Pediatrics and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; The Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, CA 94305, USA.
Kazuya MiyagawaDepartment of Pediatrics and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; The Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, CA 94305, USA.
Caiyun G LiDepartment of Pediatrics and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; The Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, CA 94305, USA.
Nils P NickelDepartment of Pediatrics and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; The Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mark KaschwichDepartment of Pediatrics and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; The Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, CA 94305, USA.
Aiqin CaoDepartment of Pediatrics and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; The Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lingli WangDepartment of Pediatrics and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; The Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sushma ReddyDepartment of Pediatrics and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Pin-I ChenDepartment of Pediatrics and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; The Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, CA 94305, USA.
Kiichi NakahiraDepartment of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
Miguel A Alejandre AlcazarDepartment of Pediatrics and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; The Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, CA 94305, USA.
Rachel K HopperDepartment of Pediatrics and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; The Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lijuan JiDepartment of Pediatrics and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Brian J FeldmanDepartment of Pediatrics and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Marlene RabinovitchDepartment of Pediatrics and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; The Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: marlener@stanford.edu.
Stanford University · USCornell University · US

Funding

Pulmonary Hypertension in Genetically Modified MiceR01HL074186 · NHLBI · STANFORD UNIVERSITY · PI RABINOVITCH, MARLENE · 2004 to 2022
$10.4M
Pulmonary Hypertension Breakthrough InitiativeR24HL123767 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI ALDRED, MICHEALA A, ERZURUM, SERPIL C. · 2014 to 2017
$10.1M
The BMP-PPARy Axis and Pulmonary HypertensionR01HL087118 · NHLBI · STANFORD UNIVERSITY · PI RABINOVITCH, MARLENE · 2008 to 2022
$7.2M
Airway redox biochemistry as a deteriminant of asthma phenotype during adolescen*U10HL109250 · NHLBI · UNIVERSITY OF VIRGINIA · PI ERZURUM, SERPIL C., GASTON, BENJAMIN · 2011 to 2016
$4.2M
Using Components of the Circadian Clock to Regulate Stem Cell Fate DecisionsDP2OD006740 · OD · STANFORD UNIVERSITY · PI FELDMAN, BRIAN J · 2010 to 2010
$2.4M
NHLBI NIH HHS R01 HL074186NHLBI NIH HHS R01 HL087118NHLBI NIH HHS R24 HL123767NHLBI NIH HHS U10 HL109250
6 · The paper itself

Abstract

Mitochondrial dysfunction, inflammation, and mutant bone morphogenetic protein receptor 2 (BMPR2) are associated with pulmonary arterial hypertension (PAH), an incurable disease characterized by pulmonary arterial (PA) endothelial cell (EC) apoptosis, decreased microvessels, and occlusive vascular remodeling. We hypothesized that reduced BMPR2 induces PAEC mitochondrial dysfunction, promoting a pro-inflammatory or pro-apoptotic state. Mice with EC deletion of BMPR2 develop hypoxia-induced pulmonary hypertension that, in contrast to non-transgenic littermates, does not reverse upon reoxygenation and is associated with reduced PA microvessels and lung EC p53, PGC1α and TFAM, regulators of mitochondrial biogenesis, and mitochondrial DNA. Decreasing PAEC BMPR2 by siRNA during reoxygenation represses p53, PGC1α, NRF2, TFAM, mitochondrial membrane potential, and ATP and induces mitochondrial DNA deletion and apoptosis. Reducing PAEC BMPR2 in normoxia increases p53, PGC1α, TFAM, mitochondrial membrane potential, ATP production, and glycolysis, and induces mitochondrial fission and a pro-inflammatory state. These features are recapitulated in PAECs from PAH patients with mutant BMPR2.

Indexed as

Models, BiologicalAnalysis of VarianceAnimalsBlotting, WesternBone Morphogenetic Protein Receptors, Type IICell SurvivalDNADNA PrimersEndothelial CellsFlow CytometryFluorescent Antibody TechniqueHEK293 CellsHumansHypertension, PulmonaryMembrane Potential, MitochondrialMiceBmpr2 protein, mouseBone Morphogenetic Protein Receptors, Type IIDNADNA PrimersRNA, Small Interfering

Identifiers

PMID25863249
PMCPMC4394191
OpenAlexW2020646157

What OpenQuestion holds

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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.