Evidence map›Paper›PMID 33322916›Full record

ArticleCirculation research2021

PPARγ-p53-Mediated Vasculoregenerative Program to Reverse Pulmonary Hypertension.

Jan K Hennigs, Aiqin Cao, Caiyun G Li, Minyi Shi, Julia Mienert, Kazuya Miyagawa, Jakob Körbelin, David P Marciano, Pin-I Chen, Matthew Roughley and 9 more

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

Article in Circulation research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
5.9field-weighted citation impact, top 3% 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

48 citing papers in PubMed, 82 citations in OpenAlex.

  1. Article
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  7. Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025
    Review
  8. [Apelin promotes proliferation, migration, and angiogenesis in bladder cancer by activating the FGF2/FGFR1 pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025
    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

19 authors at 3 institutions in 3 countries.

Jan K HennigsVera Moulton Wall Center for Pulmonary Vascular Disease (J.K.H., A.C., C.G.L., K.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W.), Stanford University School of Medicine.
Aiqin CaoVera Moulton Wall Center for Pulmonary Vascular Disease (J.K.H., A.C., C.G.L., K.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W.), Stanford University School of Medicine.
Caiyun G LiVera Moulton Wall Center for Pulmonary Vascular Disease (J.K.H., A.C., C.G.L., K.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W.), Stanford University School of Medicine.
Minyi ShiCardiovascular Institute (J.K.H., A.C., C.G.L., M.S., K.M., D.P.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W., M.P.S., M.R.), Stanford University School of Medicine.
Julia MienertDepartment of Pneumology and Center for Pulmonary Arterial Hypertension Hamburg (J.K.H., J.M., J.K.), University Medical Center Hamburg-Eppendorf, Germany.
Kazuya MiyagawaVera Moulton Wall Center for Pulmonary Vascular Disease (J.K.H., A.C., C.G.L., K.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W.), Stanford University School of Medicine.
Jakob KörbelinDepartment of Pneumology and Center for Pulmonary Arterial Hypertension Hamburg (J.K.H., J.M., J.K.), University Medical Center Hamburg-Eppendorf, Germany.
David P MarcianoCardiovascular Institute (J.K.H., A.C., C.G.L., M.S., K.M., D.P.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W., M.P.S., M.R.), Stanford University School of Medicine.
Pin-I ChenVera Moulton Wall Center for Pulmonary Vascular Disease (J.K.H., A.C., C.G.L., K.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W.), Stanford University School of Medicine.
Matthew RoughleyVera Moulton Wall Center for Pulmonary Vascular Disease (J.K.H., A.C., C.G.L., K.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W.), Stanford University School of Medicine.
Matthew V ElliottVera Moulton Wall Center for Pulmonary Vascular Disease (J.K.H., A.C., C.G.L., K.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W.), Stanford University School of Medicine.
Rebecca L HarperVera Moulton Wall Center for Pulmonary Vascular Disease (J.K.H., A.C., C.G.L., K.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W.), Stanford University School of Medicine.
Matthew A BillVera Moulton Wall Center for Pulmonary Vascular Disease (J.K.H., A.C., C.G.L., K.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W.), Stanford University School of Medicine.
James ChappellVera Moulton Wall Center for Pulmonary Vascular Disease (J.K.H., A.C., C.G.L., K.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W.), Stanford University School of Medicine.
Jan-Renier MoonenVera Moulton Wall Center for Pulmonary Vascular Disease (J.K.H., A.C., C.G.L., K.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W.), Stanford University School of Medicine.
Isabel DieboldVera Moulton Wall Center for Pulmonary Vascular Disease (J.K.H., A.C., C.G.L., K.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W.), Stanford University School of Medicine.
Lingli WangVera Moulton Wall Center for Pulmonary Vascular Disease (J.K.H., A.C., C.G.L., K.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W.), Stanford University School of Medicine.
Michael P SnyderCardiovascular Institute (J.K.H., A.C., C.G.L., M.S., K.M., D.P.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W., M.P.S., M.R.), Stanford University School of Medicine.
Marlene RabinovitchCardiovascular Institute (J.K.H., A.C., C.G.L., M.S., K.M., D.P.M., P.-I.C., M.R., M.V.E., R.L.H., M.A.B., J.C., J.-R.M., I.D., L.W., M.P.S., M.R.), Stanford University School of Medicine.
MACOM (United States) · USCardiovascular Institute of the South · USUniversität Hamburg · DE

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
Integrative Omics as a Discovery Tool for Pulmonary HypertensionR01HL122887 · NHLBI · STANFORD UNIVERSITY · PI NICOLLS, MARK ROBERT, RABINOVITCH, MARLENE · 2015 to 2018
$4.1M
Stanford Career Development Program in Omics of Lung DiseasesK12HL120001 · NHLBI · STANFORD UNIVERSITY · PI NICOLLS, MARK ROBERT, RABINOVITCH, MARLENE · 2013 to 2017
$1.3M
Metabolomic Profiling of Explanted Pulmonary Arterial Hypertension LungsF32HL132452 · NHLBI · STANFORD UNIVERSITY · PI MARCIANO, DAVID P · 2016 to 2018
$173k
NHLBI NIH HHS F32 HL132452NHLBI NIH HHS K12 HL120001NHLBI NIH HHS R01 HL074186NHLBI NIH HHS R01 HL087118NHLBI NIH HHS R01 HL122887NHLBI NIH HHS R24 HL123767
6 · The paper itself

Abstract

rationaleIn pulmonary arterial hypertension (PAH), endothelial dysfunction and obliterative vascular disease are associated with DNA damage and impaired signaling of BMPR2 (bone morphogenetic protein type 2 receptor) via two downstream transcription factors, PPARγ (peroxisome proliferator-activated receptor gamma), and p53.

objectiveWe investigated the vasculoprotective and regenerative potential of a newly identified PPARγ-p53 transcription factor complex in the pulmonary endothelium. METHODS AND

resultsIn this study, we identified a pharmacologically inducible vasculoprotective mechanism in pulmonary arterial and lung MV (microvascular) endothelial cells in response to DNA damage and oxidant stress regulated in part by a BMPR2 dependent transcription factor complex between PPARγ and p53. Chromatin immunoprecipitation sequencing and RNA-sequencing established an inducible PPARγ-p53 mediated regenerative program regulating 19 genes involved in lung endothelial cell survival, angiogenesis and DNA repair including,

conclusionsWe identified a novel therapeutic strategy that activates a vasculoprotective gene regulation program in PAECs downstream of dysfunctional BMPR2 to rehabilitate PAH PAECs, regenerate pulmonary microvessels, and reverse disease. Our studies pave the way for p53-based vasculoregenerative therapies for PAH by extending the therapeutic focus to PAEC dysfunction and to DNA damage associated with PAH progression.

Indexed as

Angiogenesis Inducing AgentsAnimalsBone Morphogenetic Protein Receptors, Type IICells, CulturedEndothelial CellsFemaleGene Expression RegulationHumansImidazolesMaleMiceMice, KnockoutNeovascularization, PhysiologicOxidative StressPiperazinesPPAR gammaAngiogenesis Inducing AgentsBmpr2 protein, mouseBone Morphogenetic Protein Receptors, Type IIImidazolesnutlin 3PiperazinesPPAR gammaPPARG protein, humanPparg protein, mouseTP53 protein, humanTrp53 protein, mouseTumor Suppressor Protein p53chromatin immunoprecipitation sequencingendotheliumepigenomicsgenes, p53hypertension, pulmonarymice

Identifiers

PMID33322916
PMCPMC7908816
OpenAlexW3111447194

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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.