Evidence map›Paper›PMID 26240367›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Endothelin receptor B, a candidate gene from human studies at high altitude, improves cardiac tolerance to hypoxia in genetically engineered heterozygote mice.

Tsering Stobdan, Dan Zhou, Eilleen Ao-Ieong, Daniel Ortiz, Roy Ronen, Iain Hartley, Zhuohui Gan, Andrew D McCulloch, Vineet Bafna, Pedro Cabrales and 1 more

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 5% 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

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

  1. Pooled it
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  10. Whole transcriptome profiling of prospective endomyocardial biopsies reveals prognostic and diagnostic signatures of cardiac allograft rejection.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2022
    Observational
  11. Article
  12. Physiological Genomics of Adaptation to High-Altitude Hypoxia.Annual review of animal biosciences · 2021
    Review
  13. Article
  14. Article
  15. Article
  16. Convergent evolution in human and domesticate adaptation to high-altitude environments.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Tsering StobdanDepartment of Pediatrics, Division of Respiratory Medicine, University of California, San Diego, La Jolla, CA 92093;
Dan ZhouDepartment of Pediatrics, Division of Respiratory Medicine, University of California, San Diego, La Jolla, CA 92093;
Eilleen Ao-IeongDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093;
Daniel OrtizDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093;
Roy RonenBioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA 92093;
Iain HartleyDepartment of Pediatrics, Division of Respiratory Medicine, University of California, San Diego, La Jolla, CA 92093;
Zhuohui GanDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093;
Andrew D McCullochDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093;
Vineet BafnaDepartment of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093;
Pedro CabralesDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093;
Gabriel G HaddadDepartment of Pediatrics, Division of Respiratory Medicine, University of California, San Diego, La Jolla, CA 92093; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093; Rady Children's Hospital, San Diego, CA 92123 ghaddad@ucsd.edu.
University of California, San Diego · USLa Jolla Bioengineering Institute · USRady Children's Hospital-San Diego · US

Funding

Recombinant HbAp Production for In Vivo Toxicity StudiesP01HL110900 · NHLBI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI FRIEDMAN, JOEL M · 2012 to 2016
$10.6M
Systems Biology CoreP01HL098053 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI POWELL, FRANK L. · 2010 to 2014
$10.2M
Integrative Bioengineering of Heart, Vessels, and BloodT32HL105373 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, INTAGLIETTA, MARCOS · 2010 to 2019
$3.6M
BLOOD FLOW AND RHEOLOGY IN THE VENOUS MICROCIRCULATIONR01HL052684 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CABRALES, PEDRO · 1996 to 2011
$3.3M
Attenuating the Oxidative and Myocardial Toxicity of Polymerized HemoglobinsR56HL123015 · NHLBI · OHIO STATE UNIVERSITY · PI CABRALES, PEDRO, PALMER, ANDRE FRANCIS · 2014 to 2014
$400k
NHLBI NIH HHS 1P01-HL098053NHLBI NIH HHS P01 HL098053NHLBI NIH HHS P01 HL110900NHLBI NIH HHS P01-HL110900NHLBI NIH HHS R01 HL052684NHLBI NIH HHS R01-HL52684NHLBI NIH HHS R56 HL123015NHLBI NIH HHS R56HL123015NHLBI NIH HHS T32 HL105373
6 · The paper itself

Abstract

To better understand human adaptation to stress, and in particular to hypoxia, we took advantage of one of nature's experiments at high altitude (HA) and studied Ethiopians, a population that is well-adapted to HA hypoxic stress. Using whole-genome sequencing, we discovered that EDNRB (Endothelin receptor type B) is a candidate gene involved in HA adaptation. To test whether EDNRB plays a critical role in hypoxia tolerance and adaptation, we generated EdnrB knockout mice and found that when EdnrB (-/+) heterozygote mice are treated with lower levels of oxygen (O2), they tolerate various levels of hypoxia (even extreme hypoxia, e.g., 5% O2) very well. For example, they maintain ejection fraction, cardiac contractility, and cardiac output in severe hypoxia. Furthermore, O2 delivery to vital organs was significantly higher and blood lactate was lower in EdnrB (-/+) compared with wild type in hypoxia. Tissue hypoxia in brain, heart, and kidney was lower in EdnrB (-/+) mice as well. These data demonstrate that a lower level of EDNRB significantly improves cardiac performance and tissue perfusion under various levels of hypoxia. Transcriptomic profiling of left ventricles revealed three specific genes [natriuretic peptide type A (Nppa), sarcolipin (Sln), and myosin light polypeptide 4 (Myl4)] that were oppositely expressed (q < 0.05) between EdnrB (-/+) and wild type. Functions related to these gene networks were consistent with a better cardiac contractility and performance. We conclude that EDNRB plays a key role in hypoxia tolerance and that a lower level of EDNRB contributes, at least in part, to HA adaptation in humans.

Indexed as

AcclimatizationAltitudeAnimalsAtrial Natriuretic FactorCardiac OutputEthiopiaFemaleHeartHeterozygoteHumansHypoxiaLactic AcidMaleMiceMice, Inbred C57BLMice, KnockoutAtrial Natriuretic FactorEDNRB protein, humanEDNRB protein, mouseLactic AcidMuscle ProteinsMYL4 protein, humanMyosin Light ChainsNPPA protein, humanOxygenProteolipidsReceptor, Endothelin Bsarcolipincardiac outputEndothelin receptor type Bhigh altitudehypoxialactate

Identifiers

PMID26240367
PMCPMC4547246
OpenAlexW2108206335

What Socratic holds

Textmetadata
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.