Evidence map›Paper›PMID 28487342›Full record

ArticleCirculation. Heart failure2017

Calcium/Calmodulin-Dependent Protein Kinase II Activity Persists During Chronic β-Adrenoceptor Blockade in Experimental and Human Heart Failure.

Matthias Dewenter, Stefan Neef, Christiane Vettel, Simon Lämmle, Christina Beushausen, Laura C Zelarayan, Sylvia Katz, Albert von der Lieth, Stefanie Meyer-Roxlau, Silvio Weber and 6 more

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Article in Circulation. Heart failure, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.9field-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

28 citing papers in PubMed, 42 citations in OpenAlex.

  1. Review
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  4. Calcineurin signaling promotes takotsubo syndrome.Nature cardiovascular research · 2023
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  8. CaMKII as a Therapeutic Target in Cardiovascular Disease.Annual review of pharmacology and toxicology · 2023
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  10. Red light-green light: T-cell trafficking in cardiac and vascular inflammation.American journal of physiology. Cell physiology · 2023
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  13. Review
  14. Chronic CaThe Journal of pharmacology and experimental therapeutics · 2021
    Article
  15. Review
  16. Review
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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

16 authors at 4 institutions in 1 country.

Matthias DewenterFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.).
Stefan NeefFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.).
Christiane VettelFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.).
Simon LämmleFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.).
Christina BeushausenFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.).
Laura C ZelarayanFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.).
Sylvia KatzFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.).
Albert von der LiethFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.).
Stefanie Meyer-RoxlauFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.).
Silvio WeberFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.).
Thomas WielandFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.).
Samuel SossallaFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.).
Johannes BacksFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.).
Joan H BrownFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.).
Lars S MaierFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.).
Ali El-ArmoucheFrom the Institute of Pharmacology (M.D., C.B., L.C.Z.) and Department of Cardiology and Pneumology (S.S.), University Medical Center Göttingen (UMG) Heart Center, Georg August University Medical School Göttingen, Germany; Department Molecular Cardiology and Epigenetics, Heidelberg University, Germany (M.D., S.K., A.v.d.L., J.B.); DZHK (German Centre for Cardiovascular Research), Partner Sites Heidelberg/Mannheim and Göttingen, Germany (M.D., C.V., C.B., L.C.Z., S.K., A.v.d.L., T.W., S.S., J.B.); Department of Internal Medicine II, University Hospital Regensburg, Germany (S.N., S.S., L.S.M.); Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Heidelberg University, Germany (C.V., T.W.); Institute of Pharmacology and Toxicology, University of Technology Dresden, Germany (S.L., S.M.-R., S.W., A.E.-A.); and Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla (J.H.B.). ali.el-armouche@tu-dresden.de.
Heidelberg University · DETU Dresden · DEUniversity Hospital Heidelberg · DEUniversity Hospital Regensburg · DE

Funding

Program AdministrationP01HL080101 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI BERS, DONALD M · 2006 to 2015
$23.4M
Multi-scale Systems Model of Murine Heart FailureR01HL105242 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BERS, DONALD M, MCCULLOCH, ANDREW D. · 2012 to 2016
$3.5M
NHLBI NIH HHS P01 HL080101NHLBI NIH HHS R01 HL105242
6 · The paper itself

Abstract

backgroundConsiderable evidence suggests that calcium/calmodulin-dependent protein kinase II (CaMKII) overactivity plays a crucial role in the pathophysiology of heart failure (HF), a condition characterized by excessive β-adrenoceptor (β-AR) stimulation. Recent studies indicate a significant cross talk between β-AR signaling and CaMKII activation presenting CaMKII as a possible downstream mediator of detrimental β-AR signaling in HF. In this study, we investigated the effect of chronic β-AR blocker treatment on CaMKII activity in human and experimental HF. METHODS AND

resultsImmunoblot analysis of myocardium from end-stage HF patients (n=12) and non-HF subjects undergoing cardiac surgery (n=12) treated with β-AR blockers revealed no difference in CaMKII activity when compared with non-β-AR blocker-treated patients. CaMKII activity was judged by analysis of CaMKII expression, autophosphorylation, and oxidation and by investigating the phosphorylation status of CaMKII downstream targets. To further evaluate these findings, CaMKIIδ

conclusionsChronic β-AR blocker therapy in patients and in a mouse model of CaMKII-induced HF is not associated with a change in CaMKII activity. Thus, our data suggest that the molecular effects of β-AR blockers are not based on a modulation of CaMKII. Directly targeting CaMKII may, therefore, further improve HF therapy in addition to β-AR blockade.

Indexed as

Adrenergic beta-AntagonistsAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Disease Models, AnimalEchocardiographyHeart FailureHumansImmunoblottingMetoprololMiceMice, TransgenicAdrenergic beta-AntagonistsCalcium-Calmodulin-Dependent Protein Kinase Type 2Metoprololbeta-adrenergic blockerscalcium/calmodulin-dependent protein kinase type 2heart failure

Identifiers

PMID28487342
PMCPMC5479434
OpenAlexW2611997071

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