Evidence map›Paper›PMID 25361553›Full record

ArticleCirculation2015

Peripheral blood signature of vasodilator-responsive pulmonary arterial hypertension.

Anna R Hemnes, Aaron W Trammell, Stephen L Archer, Stuart Rich, Chang Yu, Hui Nian, Niki Penner, Mitchell Funke, Lisa Wheeler, Ivan M Robbins and 3 more

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

Article in Circulation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 2 pooled it
5.8field-weighted citation impact, top 4% 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, 2 syntheses or guidelines pooled it, 85 citations in OpenAlex.

  1. Meta-analysis of blood genome-wide expression profiling studies in pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2020
    Pooled it
  2. Guideline
  3. Susceptibility to Childhood Pneumonia: A Genome-Wide Analysis.American journal of respiratory cell and molecular biology · 2017
    Trial
  4. Variation inCirculation research · 2026
    Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Advances in the management of pulmonary arterial hypertension.Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2021
    Review
  15. Stearoyl-CoA desaturase 5 (SCD5), a Δ-9 fatty acyl desaturase in search of a function.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Whole-Blood RNA Profiles Associated with Pulmonary Arterial Hypertension and Clinical Outcome.American journal of respiratory and critical care medicine · 2020
    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

13 authors at 2 institutions in 2 countries.

Anna R HemnesFrom the Division of Allergy, Pulmonary, and Critical Care Medicine (A.R.H., A.W.T., N.P., M.F., L.W., I.M.R., J.H.N., J.W.) and Department of Biostatistics (C.Y., H.N.), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Queen's University, Kingston, Ontario, Canada (S.L.A.); Division of Cardiology, University of Chicago, Chicago, IL (S.R.); and Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (E.D.A.). anna.r.hemnes@vanderbilt.edu.
Aaron W TrammellFrom the Division of Allergy, Pulmonary, and Critical Care Medicine (A.R.H., A.W.T., N.P., M.F., L.W., I.M.R., J.H.N., J.W.) and Department of Biostatistics (C.Y., H.N.), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Queen's University, Kingston, Ontario, Canada (S.L.A.); Division of Cardiology, University of Chicago, Chicago, IL (S.R.); and Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (E.D.A.).
Stephen L ArcherFrom the Division of Allergy, Pulmonary, and Critical Care Medicine (A.R.H., A.W.T., N.P., M.F., L.W., I.M.R., J.H.N., J.W.) and Department of Biostatistics (C.Y., H.N.), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Queen's University, Kingston, Ontario, Canada (S.L.A.); Division of Cardiology, University of Chicago, Chicago, IL (S.R.); and Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (E.D.A.).
Stuart RichFrom the Division of Allergy, Pulmonary, and Critical Care Medicine (A.R.H., A.W.T., N.P., M.F., L.W., I.M.R., J.H.N., J.W.) and Department of Biostatistics (C.Y., H.N.), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Queen's University, Kingston, Ontario, Canada (S.L.A.); Division of Cardiology, University of Chicago, Chicago, IL (S.R.); and Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (E.D.A.).
Chang YuFrom the Division of Allergy, Pulmonary, and Critical Care Medicine (A.R.H., A.W.T., N.P., M.F., L.W., I.M.R., J.H.N., J.W.) and Department of Biostatistics (C.Y., H.N.), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Queen's University, Kingston, Ontario, Canada (S.L.A.); Division of Cardiology, University of Chicago, Chicago, IL (S.R.); and Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (E.D.A.).
Hui NianFrom the Division of Allergy, Pulmonary, and Critical Care Medicine (A.R.H., A.W.T., N.P., M.F., L.W., I.M.R., J.H.N., J.W.) and Department of Biostatistics (C.Y., H.N.), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Queen's University, Kingston, Ontario, Canada (S.L.A.); Division of Cardiology, University of Chicago, Chicago, IL (S.R.); and Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (E.D.A.).
Niki PennerFrom the Division of Allergy, Pulmonary, and Critical Care Medicine (A.R.H., A.W.T., N.P., M.F., L.W., I.M.R., J.H.N., J.W.) and Department of Biostatistics (C.Y., H.N.), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Queen's University, Kingston, Ontario, Canada (S.L.A.); Division of Cardiology, University of Chicago, Chicago, IL (S.R.); and Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (E.D.A.).
Mitchell FunkeFrom the Division of Allergy, Pulmonary, and Critical Care Medicine (A.R.H., A.W.T., N.P., M.F., L.W., I.M.R., J.H.N., J.W.) and Department of Biostatistics (C.Y., H.N.), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Queen's University, Kingston, Ontario, Canada (S.L.A.); Division of Cardiology, University of Chicago, Chicago, IL (S.R.); and Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (E.D.A.).
Lisa WheelerFrom the Division of Allergy, Pulmonary, and Critical Care Medicine (A.R.H., A.W.T., N.P., M.F., L.W., I.M.R., J.H.N., J.W.) and Department of Biostatistics (C.Y., H.N.), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Queen's University, Kingston, Ontario, Canada (S.L.A.); Division of Cardiology, University of Chicago, Chicago, IL (S.R.); and Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (E.D.A.).
Ivan M RobbinsFrom the Division of Allergy, Pulmonary, and Critical Care Medicine (A.R.H., A.W.T., N.P., M.F., L.W., I.M.R., J.H.N., J.W.) and Department of Biostatistics (C.Y., H.N.), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Queen's University, Kingston, Ontario, Canada (S.L.A.); Division of Cardiology, University of Chicago, Chicago, IL (S.R.); and Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (E.D.A.).
Eric D AustinFrom the Division of Allergy, Pulmonary, and Critical Care Medicine (A.R.H., A.W.T., N.P., M.F., L.W., I.M.R., J.H.N., J.W.) and Department of Biostatistics (C.Y., H.N.), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Queen's University, Kingston, Ontario, Canada (S.L.A.); Division of Cardiology, University of Chicago, Chicago, IL (S.R.); and Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (E.D.A.).
John H NewmanFrom the Division of Allergy, Pulmonary, and Critical Care Medicine (A.R.H., A.W.T., N.P., M.F., L.W., I.M.R., J.H.N., J.W.) and Department of Biostatistics (C.Y., H.N.), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Queen's University, Kingston, Ontario, Canada (S.L.A.); Division of Cardiology, University of Chicago, Chicago, IL (S.R.); and Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (E.D.A.).
James WestFrom the Division of Allergy, Pulmonary, and Critical Care Medicine (A.R.H., A.W.T., N.P., M.F., L.W., I.M.R., J.H.N., J.W.) and Department of Biostatistics (C.Y., H.N.), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Queen's University, Kingston, Ontario, Canada (S.L.A.); Division of Cardiology, University of Chicago, Chicago, IL (S.R.); and Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (E.D.A.).
Queen's University · CAUniversity of Chicago · US

Funding

The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
Sex Hormones in Pulmonary Arterial HypertensionP01HL108800 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI LOYD, JAMES E · 2012 to 2021
$22.0M
Re-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2M
Interventions Against the Molecular Etiology of BMPR2-induced PAHR01HL095797 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WEST, JAMES D · 2010 to 2022
$6.7M
Caveolar Defects Underlie the Genetic Origins of PAHR01HL111259 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI KENWORTHY, ANNE K, LOYD, JAMES E · 2012 to 2016
$3.5M
O2 sensing in the human and rabbit ductus arteriosus.R01HL071115 · NHLBI · UNIVERSITY OF CHICAGO · PI ARCHER, STEPHEN L · 2004 to 2015
$3.1M
The Role of DRP-1 and Mitochondrial Fission in Pulmonary Arterial HypertensionR01HL113003 · NHLBI · QUEEN'S UNIVERSITY AT KINGSTON · PI ARCHER, STEPHEN L · 2013 to 2016
$1.1M
Impaired mitochondrial fusion in pulmonary arterial hypertensionRC1HL099462 · NHLBI · UNIVERSITY OF CHICAGO · PI ARCHER, STEPHEN L · 2009 to 2010
$1.0M
Gender differences and endothelin responses in right ventricular afterload stressK08HL093363 · NHLBI · VANDERBILT UNIVERSITY · PI HEMNES, ANNA R · 2008 to 2012
$627k
NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1TR000445NHLBI NIH HHS 1 K08 HL 093363NHLBI NIH HHS 1 P01 HL 108800NHLBI NIH HHS 1RC1HL099462NHLBI NIH HHS K08 HL093363NHLBI NIH HHS P01 HL108800NHLBI NIH HHS R01 HL071115NHLBI NIH HHS R01-HL071115NHLBI NIH HHS R01 HL095797NHLBI NIH HHS RC1 HL099462
6 · The paper itself

Abstract

backgroundHeterogeneity in response to treatment of pulmonary arterial hypertension (PAH) is a major challenge to improving outcome in this disease. Although vasodilator-responsive PAH (VR-PAH) accounts for a minority of cases, VR-PAH has a pronounced response to calcium channel blockers and better survival than vasodilator-nonresponsive PAH (VN-PAH). We hypothesized that VR-PAH has a different molecular cause from VN-PAH that can be detected in the peripheral blood. METHODS AND

resultsMicroarrays of cultured lymphocytes from VR-PAH and VN-PAH patients followed at Vanderbilt University were performed with quantitative polymerase chain reaction performed on peripheral blood for the 25 most different genes. We developed a decision tree to identify VR-PAH patients on the basis of the results with validation in a second VR-PAH cohort from the University of Chicago. We found broad differences in gene expression patterns on microarray analysis including cell-cell adhesion factors and cytoskeletal and rho-GTPase genes. Thirteen of 25 genes tested in whole blood were significantly different: EPDR1, DSG2, SCD5, P2RY5, MGAT5, RHOQ, UCHL1, ZNF652, RALGPS2, TPD52, MKNL1, RAPGEF2, and PIAS1. Seven decision trees were built with the use of expression levels of 2 genes as the primary genes: DSG2, a desmosomal cadherin involved in Wnt/β-catenin signaling, and RHOQ, which encodes a cytoskeletal protein involved in insulin-mediated signaling. These trees correctly identified 5 of 5 VR-PAH patients in the validation cohort.

conclusionsVR-PAH and VN-PAH can be differentiated with the use of RNA expression patterns in peripheral blood. These differences may reflect different molecular causes of the 2 PAH phenotypes. This biomarker methodology may identify PAH patients who have a favorable treatment response.

Indexed as

AdolescentAdultCells, CulturedCohort StudiesFemaleHumansHypertension, PulmonaryLymphocytesMaleMicroarray AnalysisMiddle AgedVasodilationYoung Adultbiomarkerspulmonary hypertensiontreatment

Identifiers

PMID25361553
PMCPMC4308423
OpenAlexW1975889620

What OpenQuestion holds

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Read underepoch 390

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.