Evidence map›Paper›PMID 27364164›Full record

ArticleCirculation2016

Leukocyte-Expressed β2-Adrenergic Receptors Are Essential for Survival After Acute Myocardial Injury.

Laurel A Grisanti, Anna M Gumpert, Christopher J Traynham, Joshua E Gorsky, Ashley A Repas, Erhe Gao, Rhonda L Carter, Daohai Yu, John W Calvert, Andrés Pun García and 4 more

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

Article in Circulation, 2016. 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
5.6field-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, 68 citations in OpenAlex.

  1. Review
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  7. The spleen in ischaemic heart disease.Nature reviews. Cardiology · 2025
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  13. Review
  14. Article
  15. Article
  16. Article
  17. Macrophages Remember When Your Heart Was Broken.JACC. Basic to translational science · 2023
    Article
  18. Quo Vadis? Immunodynamics of Myeloid Cells after Myocardial Infarction.International journal of molecular sciences · 2022
    Review
  19. Article
  20. Immune remodeling and atrial fibrillation.Frontiers in physiology · 2022
    Review
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 1 institution in 1 country.

Laurel A GrisantiFrom Center for Translational Medicine (L.A.G., A.M.G., C.J.T., J.E.G., A.A.R., E.G., R.L.C., J.E.R., W.J.K., D.G.T.), Department of Pharmacology (E.G., J.E.R., W.J.K., D.G.T.), and Department of Clinical Sciences (D.Y.), Temple University School of Medicine, Philadelphia, PA; Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine and Carlyle Fraser Heart Center, Atlanta, GA (J.W.C.); and Spanish National Center for Cardiovascular Research, Madrid, Spain (A.P.G., B.I.).
Anna M GumpertFrom Center for Translational Medicine (L.A.G., A.M.G., C.J.T., J.E.G., A.A.R., E.G., R.L.C., J.E.R., W.J.K., D.G.T.), Department of Pharmacology (E.G., J.E.R., W.J.K., D.G.T.), and Department of Clinical Sciences (D.Y.), Temple University School of Medicine, Philadelphia, PA; Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine and Carlyle Fraser Heart Center, Atlanta, GA (J.W.C.); and Spanish National Center for Cardiovascular Research, Madrid, Spain (A.P.G., B.I.).
Christopher J TraynhamFrom Center for Translational Medicine (L.A.G., A.M.G., C.J.T., J.E.G., A.A.R., E.G., R.L.C., J.E.R., W.J.K., D.G.T.), Department of Pharmacology (E.G., J.E.R., W.J.K., D.G.T.), and Department of Clinical Sciences (D.Y.), Temple University School of Medicine, Philadelphia, PA; Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine and Carlyle Fraser Heart Center, Atlanta, GA (J.W.C.); and Spanish National Center for Cardiovascular Research, Madrid, Spain (A.P.G., B.I.).
Joshua E GorskyFrom Center for Translational Medicine (L.A.G., A.M.G., C.J.T., J.E.G., A.A.R., E.G., R.L.C., J.E.R., W.J.K., D.G.T.), Department of Pharmacology (E.G., J.E.R., W.J.K., D.G.T.), and Department of Clinical Sciences (D.Y.), Temple University School of Medicine, Philadelphia, PA; Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine and Carlyle Fraser Heart Center, Atlanta, GA (J.W.C.); and Spanish National Center for Cardiovascular Research, Madrid, Spain (A.P.G., B.I.).
Ashley A RepasFrom Center for Translational Medicine (L.A.G., A.M.G., C.J.T., J.E.G., A.A.R., E.G., R.L.C., J.E.R., W.J.K., D.G.T.), Department of Pharmacology (E.G., J.E.R., W.J.K., D.G.T.), and Department of Clinical Sciences (D.Y.), Temple University School of Medicine, Philadelphia, PA; Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine and Carlyle Fraser Heart Center, Atlanta, GA (J.W.C.); and Spanish National Center for Cardiovascular Research, Madrid, Spain (A.P.G., B.I.).
Erhe GaoFrom Center for Translational Medicine (L.A.G., A.M.G., C.J.T., J.E.G., A.A.R., E.G., R.L.C., J.E.R., W.J.K., D.G.T.), Department of Pharmacology (E.G., J.E.R., W.J.K., D.G.T.), and Department of Clinical Sciences (D.Y.), Temple University School of Medicine, Philadelphia, PA; Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine and Carlyle Fraser Heart Center, Atlanta, GA (J.W.C.); and Spanish National Center for Cardiovascular Research, Madrid, Spain (A.P.G., B.I.).
Rhonda L CarterFrom Center for Translational Medicine (L.A.G., A.M.G., C.J.T., J.E.G., A.A.R., E.G., R.L.C., J.E.R., W.J.K., D.G.T.), Department of Pharmacology (E.G., J.E.R., W.J.K., D.G.T.), and Department of Clinical Sciences (D.Y.), Temple University School of Medicine, Philadelphia, PA; Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine and Carlyle Fraser Heart Center, Atlanta, GA (J.W.C.); and Spanish National Center for Cardiovascular Research, Madrid, Spain (A.P.G., B.I.).
Daohai YuFrom Center for Translational Medicine (L.A.G., A.M.G., C.J.T., J.E.G., A.A.R., E.G., R.L.C., J.E.R., W.J.K., D.G.T.), Department of Pharmacology (E.G., J.E.R., W.J.K., D.G.T.), and Department of Clinical Sciences (D.Y.), Temple University School of Medicine, Philadelphia, PA; Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine and Carlyle Fraser Heart Center, Atlanta, GA (J.W.C.); and Spanish National Center for Cardiovascular Research, Madrid, Spain (A.P.G., B.I.).
John W CalvertFrom Center for Translational Medicine (L.A.G., A.M.G., C.J.T., J.E.G., A.A.R., E.G., R.L.C., J.E.R., W.J.K., D.G.T.), Department of Pharmacology (E.G., J.E.R., W.J.K., D.G.T.), and Department of Clinical Sciences (D.Y.), Temple University School of Medicine, Philadelphia, PA; Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine and Carlyle Fraser Heart Center, Atlanta, GA (J.W.C.); and Spanish National Center for Cardiovascular Research, Madrid, Spain (A.P.G., B.I.).
Andrés Pun GarcíaFrom Center for Translational Medicine (L.A.G., A.M.G., C.J.T., J.E.G., A.A.R., E.G., R.L.C., J.E.R., W.J.K., D.G.T.), Department of Pharmacology (E.G., J.E.R., W.J.K., D.G.T.), and Department of Clinical Sciences (D.Y.), Temple University School of Medicine, Philadelphia, PA; Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine and Carlyle Fraser Heart Center, Atlanta, GA (J.W.C.); and Spanish National Center for Cardiovascular Research, Madrid, Spain (A.P.G., B.I.).
Borja IbáñezFrom Center for Translational Medicine (L.A.G., A.M.G., C.J.T., J.E.G., A.A.R., E.G., R.L.C., J.E.R., W.J.K., D.G.T.), Department of Pharmacology (E.G., J.E.R., W.J.K., D.G.T.), and Department of Clinical Sciences (D.Y.), Temple University School of Medicine, Philadelphia, PA; Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine and Carlyle Fraser Heart Center, Atlanta, GA (J.W.C.); and Spanish National Center for Cardiovascular Research, Madrid, Spain (A.P.G., B.I.).
Joseph E RabinowitzFrom Center for Translational Medicine (L.A.G., A.M.G., C.J.T., J.E.G., A.A.R., E.G., R.L.C., J.E.R., W.J.K., D.G.T.), Department of Pharmacology (E.G., J.E.R., W.J.K., D.G.T.), and Department of Clinical Sciences (D.Y.), Temple University School of Medicine, Philadelphia, PA; Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine and Carlyle Fraser Heart Center, Atlanta, GA (J.W.C.); and Spanish National Center for Cardiovascular Research, Madrid, Spain (A.P.G., B.I.).
Walter J KochFrom Center for Translational Medicine (L.A.G., A.M.G., C.J.T., J.E.G., A.A.R., E.G., R.L.C., J.E.R., W.J.K., D.G.T.), Department of Pharmacology (E.G., J.E.R., W.J.K., D.G.T.), and Department of Clinical Sciences (D.Y.), Temple University School of Medicine, Philadelphia, PA; Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine and Carlyle Fraser Heart Center, Atlanta, GA (J.W.C.); and Spanish National Center for Cardiovascular Research, Madrid, Spain (A.P.G., B.I.).
Douglas G TilleyFrom Center for Translational Medicine (L.A.G., A.M.G., C.J.T., J.E.G., A.A.R., E.G., R.L.C., J.E.R., W.J.K., D.G.T.), Department of Pharmacology (E.G., J.E.R., W.J.K., D.G.T.), and Department of Clinical Sciences (D.Y.), Temple University School of Medicine, Philadelphia, PA; Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine and Carlyle Fraser Heart Center, Atlanta, GA (J.W.C.); and Spanish National Center for Cardiovascular Research, Madrid, Spain (A.P.G., B.I.). douglas.tilley@temple.edu.
Emory University Hospital Midtown · US

Funding

Targeted Cancer Therapeutics and Heart Failure: Mechanisms and Post-injury RepairP01HL091799 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI KOCH, WALTER J. · 2008 to 2018
$23.1M
Molecular Mechanisms of Cardiac beta1AR-EGFR Association and SignalingR01HL105414 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI TILLEY, DOUGLAS · 2011 to 2019
$3.4M
GRK and b-Arrestin Signaling in Cardiac RegenerationR01HL085503 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI KOCH, WALTER J. · 2007 to 2015
$3.0M
Hydrogen sulfide attenuates heart failure through Nrf2-mediated signalingR01HL098481 · NHLBI · EMORY UNIVERSITY · PI CALVERT, JOHN WINTER · 2010 to 2014
$1.9M
NHLBI NIH HHS P01 HL091799NHLBI NIH HHS R01 HL085503NHLBI NIH HHS R01 HL098481NHLBI NIH HHS R01 HL105414
6 · The paper itself

Abstract

backgroundImmune cell-mediated inflammation is an essential process for mounting a repair response after myocardial infarction (MI). The sympathetic nervous system is known to regulate immune system function through β-adrenergic receptors (βARs); however, their role in regulating immune cell responses to acute cardiac injury is unknown.

methodsWild-type (WT) mice were irradiated followed by isoform-specific βAR knockout (βARKO) or WT bone-marrow transplantation (BMT) and after full reconstitution underwent MI surgery. Survival was monitored over time, and alterations in immune cell infiltration after MI were examined through immunohistochemistry. Alterations in splenic function were identified through the investigation of altered adhesion receptor expression.

resultsβ2ARKO BMT mice displayed 100% mortality resulting from cardiac rupture within 12 days after MI compared with ≈20% mortality in WT BMT mice. β2ARKO BMT mice displayed severely reduced post-MI cardiac infiltration of leukocytes with reciprocally enhanced splenic retention of the same immune cell populations. Splenic retention of the leukocytes was associated with an increase in vascular cell adhesion molecule-1 expression, which itself was regulated via β-arrestin-dependent β2AR signaling. Furthermore, vascular cell adhesion molecule-1 expression in both mouse and human macrophages was sensitive to β2AR activity, and spleens from human tissue donors treated with β-blocker showed enhanced vascular cell adhesion molecule-1 expression. The impairments in splenic retention and cardiac infiltration of leukocytes after MI were restored to WT levels via lentiviral-mediated re-expression of β2AR in β2ARKO bone marrow before transplantation, which also resulted in post-MI survival rates comparable to those in WT BMT mice.

conclusionsImmune cell-expressed β2AR plays an essential role in regulating the early inflammatory repair response to acute myocardial injury by facilitating cardiac leukocyte infiltration.

Indexed as

AgedAged, 80 and overAnimalsDisease Models, AnimalFemaleGenetic VectorsHeart RuptureHumansLeukocytesMacrophagesMaleMetoprololMiceMice, Inbred C57BLMyocardial InfarctionNeutrophil InfiltrationMetoprololReceptors, Adrenergic, beta-2Recombinant Fusion ProteinsVascular Cell Adhesion Molecule-1immune systeminflammationleukocytesmyocardial infarction

Identifiers

PMID27364164
PMCPMC5120587
OpenAlexW2472492028

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.