Evidence map›Paper›PMID 26850880›Full record

ArticleCirculation. Arrhythmia and electrophysiology2016

Characterizing the Molecular Pathology of Arrhythmogenic Cardiomyopathy in Patient Buccal Mucosa Cells.

Angeliki Asimaki, Alexandros Protonotarios, Cynthia A James, Stephen P Chelko, Crystal Tichnell, Brittney Murray, Adalena Tsatsopoulou, Aris Anastasakis, Anneline te Riele, André G Kléber and 3 more

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

Article in Circulation. Arrhythmia and electrophysiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

29 citing papers in PubMed, 47 citations in OpenAlex.

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  12. Genetic predisposition study of heart failure and its association with cardiomyopathy.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2022
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  18. Risk stratification and subclinical phenotyping of dilated and/or arrhythmogenic cardiomyopathy mutation-positive relatives: CVON eDETECT consortium.Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation · 2021
    Review
  19. Review
  20. Human Cell Modeling for Cardiovascular Diseases.International journal of molecular sciences · 2020
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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

13 authors at 4 institutions in 1 country.

Angeliki AsimakiFrom the Department of Pathology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA (A. Asimaki, A.G.K., J.E.S.); Nikos Protonotarios Medical Center, Naxos, Greece (A.P., A.T.); Department of Medicine/Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (C.A.J., S.P.C., C.T., B.M., A.t.R., D.P.J., H.C.); and First Department of Cardiology, University of Athens Medical School, Athens, Greece (A. Anastasakis).
Alexandros ProtonotariosFrom the Department of Pathology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA (A. Asimaki, A.G.K., J.E.S.); Nikos Protonotarios Medical Center, Naxos, Greece (A.P., A.T.); Department of Medicine/Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (C.A.J., S.P.C., C.T., B.M., A.t.R., D.P.J., H.C.); and First Department of Cardiology, University of Athens Medical School, Athens, Greece (A. Anastasakis).
Cynthia A JamesFrom the Department of Pathology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA (A. Asimaki, A.G.K., J.E.S.); Nikos Protonotarios Medical Center, Naxos, Greece (A.P., A.T.); Department of Medicine/Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (C.A.J., S.P.C., C.T., B.M., A.t.R., D.P.J., H.C.); and First Department of Cardiology, University of Athens Medical School, Athens, Greece (A. Anastasakis).
Stephen P ChelkoFrom the Department of Pathology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA (A. Asimaki, A.G.K., J.E.S.); Nikos Protonotarios Medical Center, Naxos, Greece (A.P., A.T.); Department of Medicine/Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (C.A.J., S.P.C., C.T., B.M., A.t.R., D.P.J., H.C.); and First Department of Cardiology, University of Athens Medical School, Athens, Greece (A. Anastasakis).
Crystal TichnellFrom the Department of Pathology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA (A. Asimaki, A.G.K., J.E.S.); Nikos Protonotarios Medical Center, Naxos, Greece (A.P., A.T.); Department of Medicine/Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (C.A.J., S.P.C., C.T., B.M., A.t.R., D.P.J., H.C.); and First Department of Cardiology, University of Athens Medical School, Athens, Greece (A. Anastasakis).
Brittney MurrayFrom the Department of Pathology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA (A. Asimaki, A.G.K., J.E.S.); Nikos Protonotarios Medical Center, Naxos, Greece (A.P., A.T.); Department of Medicine/Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (C.A.J., S.P.C., C.T., B.M., A.t.R., D.P.J., H.C.); and First Department of Cardiology, University of Athens Medical School, Athens, Greece (A. Anastasakis).
Adalena TsatsopoulouFrom the Department of Pathology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA (A. Asimaki, A.G.K., J.E.S.); Nikos Protonotarios Medical Center, Naxos, Greece (A.P., A.T.); Department of Medicine/Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (C.A.J., S.P.C., C.T., B.M., A.t.R., D.P.J., H.C.); and First Department of Cardiology, University of Athens Medical School, Athens, Greece (A. Anastasakis).
Aris AnastasakisFrom the Department of Pathology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA (A. Asimaki, A.G.K., J.E.S.); Nikos Protonotarios Medical Center, Naxos, Greece (A.P., A.T.); Department of Medicine/Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (C.A.J., S.P.C., C.T., B.M., A.t.R., D.P.J., H.C.); and First Department of Cardiology, University of Athens Medical School, Athens, Greece (A. Anastasakis).
Anneline te RieleFrom the Department of Pathology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA (A. Asimaki, A.G.K., J.E.S.); Nikos Protonotarios Medical Center, Naxos, Greece (A.P., A.T.); Department of Medicine/Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (C.A.J., S.P.C., C.T., B.M., A.t.R., D.P.J., H.C.); and First Department of Cardiology, University of Athens Medical School, Athens, Greece (A. Anastasakis).
André G KléberFrom the Department of Pathology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA (A. Asimaki, A.G.K., J.E.S.); Nikos Protonotarios Medical Center, Naxos, Greece (A.P., A.T.); Department of Medicine/Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (C.A.J., S.P.C., C.T., B.M., A.t.R., D.P.J., H.C.); and First Department of Cardiology, University of Athens Medical School, Athens, Greece (A. Anastasakis).
Daniel P JudgeFrom the Department of Pathology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA (A. Asimaki, A.G.K., J.E.S.); Nikos Protonotarios Medical Center, Naxos, Greece (A.P., A.T.); Department of Medicine/Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (C.A.J., S.P.C., C.T., B.M., A.t.R., D.P.J., H.C.); and First Department of Cardiology, University of Athens Medical School, Athens, Greece (A. Anastasakis).
Hugh CalkinsFrom the Department of Pathology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA (A. Asimaki, A.G.K., J.E.S.); Nikos Protonotarios Medical Center, Naxos, Greece (A.P., A.T.); Department of Medicine/Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (C.A.J., S.P.C., C.T., B.M., A.t.R., D.P.J., H.C.); and First Department of Cardiology, University of Athens Medical School, Athens, Greece (A. Anastasakis).
Jeffrey E SaffitzFrom the Department of Pathology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA (A. Asimaki, A.G.K., J.E.S.); Nikos Protonotarios Medical Center, Naxos, Greece (A.P., A.T.); Department of Medicine/Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (C.A.J., S.P.C., C.T., B.M., A.t.R., D.P.J., H.C.); and First Department of Cardiology, University of Athens Medical School, Athens, Greece (A. Anastasakis). jsaffitz@bidmc.harvard.edu.
Harvard University · USBeth Israel Deaconess Medical Center · USJohns Hopkins Medicine · USJohns Hopkins University · US

Funding

Genetics, Mechanisms and Clinical Phenotypes of Arrhythmogenic CardiomyopathyR01HL116906 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI MARCUS, FRANK I, MESTRONI, LUISA · 2013 to 2016
$9.2M
NHLBI NIH HHS HL116906NHLBI NIH HHS R01 HL116906
6 · The paper itself

Abstract

backgroundAnalysis of myocardium has revealed mechanistic insights into arrhythmogenic cardiomyopathy but cardiac samples are difficult to obtain from probands and especially from family members. To identify a potential surrogate tissue, we characterized buccal mucosa cells. METHODS AND

resultsBuccal cells from patients, mutation carriers, and controls were immunostained and analyzed in a blinded fashion. In additional studies, buccal cells were grown in vitro and incubated with SB216763. Immunoreactive signals for the desmosomal protein plakoglobin and the major cardiac gap junction protein Cx43 were markedly diminished in buccal mucosa cells from arrhythmogenic cardiomyopathy patients with known desmosomal mutations when compared with controls. Plakoglobin and Cx43 signals were also reduced in most family members who carried disease alleles but showed no evidence of heart disease. Signal for the desmosomal protein plakophilin-1 was reduced in buccal mucosa cells in patients with PKP2 mutations but not in those with mutations in other desmosomal genes. Signal for the desmosomal protein desmoplakin was reduced in buccal mucosa cells from patients with mutations in DSP, DSG2, or DSC2 but not in PKP2 or JUP. Abnormal protein distributions were reversed in cultured cells incubated with SB216763, a small molecule that rescues the disease phenotype in cardiac myocytes.

conclusionsBuccal mucosa cells from arrhythmogenic cardiomyopathy patients exhibit changes in the distribution of cell junction proteins similar to those seen in the heart. These cells may prove useful in future studies of disease mechanisms and drug screens for effective therapies in arrhythmogenic cardiomyopathy.

Indexed as

Arrhythmogenic Right Ventricular DysplasiaBaltimoreBostonCase-Control StudiesCells, CulturedConnexin 43DesmocollinsDesmoglein 2DesmoplakinsDNA Mutational AnalysisEpithelial Cellsgamma CateninGenetic Predisposition to DiseaseGreeceHumansImmunohistochemistryConnexin 43DesmocollinsDesmoglein 2DesmoplakinsDSC2 protein, humanDSG2 protein, humanDSP protein, humangamma CateninGJA1 protein, humanJUP protein, humanPKP2 protein, humanPlakophilinsarrhythmogenic right ventricular cardiomyopathybuccal mucosa cellsconnexin43desmosome cardiomyopathydiagnosisplakoglobin

Identifiers

PMID26850880
PMCPMC4785796
OpenAlexW2266702408

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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.