Evidence map›Paper›PMID 26464333›Full record

ArticleCardiovascular research2015

Lack of Gαi2 leads to dilative cardiomyopathy and increased mortality in β1-adrenoceptor overexpressing mice.

Kirsten Keller, Martina Maass, Sara Dizayee, Veronika Leiss, Suvi Annala, Jessica Köth, Wiebke K Seemann, Jochen Müller-Ehmsen, Klaus Mohr, Bernd Nürnberg and 4 more

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In one paragraph

Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.3field-weighted citation impact, top 38% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. GαInternational journal of molecular sciences · 2025
    Article
  2. Opposite effects of GαNaunyn-Schmiedeberg's archives of pharmacology · 2025
    Article
  3. Protective effects of GαNaunyn-Schmiedeberg's archives of pharmacology · 2024
    Article
  4. Review
  5. Article
  6. 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

14 authors at 7 institutions in 2 countries.

Kirsten KellerDepartment of Pharmacology, University of Cologne, Gleueler Strasse 24, 50931 Cologne, Germany.
Martina MaassDepartment of Internal Medicine III, University Hospital of Cologne, Cologne, Germany.
Sara DizayeeDepartment of Pharmacology, University of Cologne, Gleueler Strasse 24, 50931 Cologne, Germany.
Veronika LeissDepartment of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, and Interfaculty Center of Pharmacogenomics and Drug Research, Tuebingen, Germany.
Suvi AnnalaDepartment of Pharmacology, University of Cologne, Gleueler Strasse 24, 50931 Cologne, Germany.
Jessica KöthDepartment of Pharmacology, University of Cologne, Gleueler Strasse 24, 50931 Cologne, Germany.
Wiebke K SeemannDepartment of Pharmacology, University of Cologne, Gleueler Strasse 24, 50931 Cologne, Germany.
Jochen Müller-EhmsenAsklepios Klinik Altona, Hamburg, Germany.
Klaus MohrPharmacology and Toxicology Section, Institute of Pharmacy, University of Bonn, Bonn, Germany.
Bernd NürnbergDepartment of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, and Interfaculty Center of Pharmacogenomics and Drug Research, Tuebingen, Germany.
Stefan EngelhardtInstitute of Pharmacology and Toxicology, Technische Universität München, Munich, Germany.
Stefan HerzigDepartment of Pharmacology, University of Cologne, Gleueler Strasse 24, 50931 Cologne, Germany.
Lutz BirnbaumerLaboratory of Neurobiology, NIEHS, NIH (Department of Health and Human Services), Durham, USA.
Jan MatthesDepartment of Pharmacology, University of Cologne, Gleueler Strasse 24, 50931 Cologne, Germany jan.matthes@uni-koeln.de.
University of Cologne · DEUniversity of Tübingen · DEAsklepios Klinik Altona · DENational Institute of Environmental Health Sciences · USTechnical University of Munich · DEUniversity Hospital Cologne · DEUniversity of Bonn · DE

Funding

Transmembrane Signaling MechanismsZ01ES101643 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI BIRNBAUMER, LUTZ · 2003 to 2008
$5.1M
NIEHS NIH HHS Z01-ES-101643
6 · The paper itself

Abstract

aimsInhibitory G (Gi) proteins have been proposed to be cardioprotective. We investigated effects of Gαi2 knockout on cardiac function and survival in a murine heart failure model of cardiac β1-adrenoceptor overexpression. METHODS AND

resultsβ1-transgenic mice lacking Gαi2 (β1-tg/Gαi2 (-/-)) were compared with wild-type mice and littermates either overexpressing cardiac β1-adrenoceptors (β1-tg) or lacking Gαi2 (Gαi2 (-/-)). At 300 days, mortality of mice only lacking Gαi2 was already higher compared with wild-type or β1-tg, but similar to β1-tg/Gαi2 (-/-), mice. Beyond 300 days, mortality of β1-tg/Gαi2 (-/-) mice was enhanced compared with all other genotypes (mean survival time: 363 ± 21 days). At 300 days of age, echocardiography revealed similar cardiac function of wild-type, β1-tg, and Gαi2 (-/-) mice, but significant impairment for β1-tg/Gαi2 (-/-) mice (e.g. ejection fraction 14 ± 2 vs. 40 ± 4% in wild-type mice). Significantly increased ventricle-to-body weight ratio (0.71 ± 0.06 vs. 0.48 ± 0.02% in wild-type mice), left ventricular size (length 0.82 ± 0.04 vs. 0.66 ± 0.03 cm in wild types), and atrial natriuretic peptide and brain natriuretic peptide expression (mRNA: 2819 and 495% of wild-type mice, respectively) indicated hypertrophy. Gαi3 was significantly up-regulated in Gαi2 knockout mice (protein compared with wild type: 340 ± 90% in Gαi2 (-/-) and 394 ± 80% in β1-tg/Gαi2 (-/-), respectively).

conclusionsGαi2 deficiency combined with cardiac β1-adrenoceptor overexpression strongly impaired survival and cardiac function. At 300 days of age, β1-adrenoceptor overexpression alone had not induced cardiac hypertrophy or dysfunction while there was overt cardiomyopathy in mice additionally lacking Gαi2. We propose an enhanced effect of increased β1-adrenergic drive by the lack of protection via Gαi2. Gαi3 up-regulation was not sufficient to compensate for Gαi2 deficiency, suggesting an isoform-specific or a concentration-dependent mechanism.

Indexed as

AnimalsAtrial Natriuretic FactorCardiomyopathy, DilatedCyclic AMPCyclic AMP-Dependent Protein KinasesDisease Models, AnimalGene Expression RegulationGenetic Predisposition to DiseaseGTP-Binding Protein alpha Subunit, Gi2GTP-Binding Protein alpha Subunits, Gi-GoHeart FailureMice, 129 StrainMice, Inbred C57BLMice, KnockoutMyocytes, CardiacNatriuretic Peptide, BrainAdrb1 protein, mouseAtrial Natriuretic FactorCyclic AMPCyclic AMP-Dependent Protein KinasesGnai2 protein, mouseGnai3 protein, mouseGTP-Binding Protein alpha Subunit, Gi2GTP-Binding Protein alpha Subunits, Gi-GoNatriuretic Peptide, BrainReceptors, Adrenergic, beta-1Adrenergic receptorCardiomyopathyCardioprotectionHeart failureInhibitory G protein

Identifiers

PMID26464333
PMCPMC4648201
OpenAlexW2117327462

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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.