Evidence map›Paper›PMID 36424000›Full record

ArticleJACC. Clinical electrophysiology2022

Molecular and Functional Remodeling of Superior and Inferior SAN in a Rat Model of HCM.

Anna Gams, Jaclyn A Brennan, Katherine Goldrick, Igor R Efimov

Abstract read
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In one paragraph

Article in JACC. Clinical electrophysiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 23% 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

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Aging and sinus node dysfunction: mechanisms and future directions.Clinical science (London, England : 1979) · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Anna GamsDepartment of Biomedical Engineering, The George Washington University, Washington, DC, USA.
Jaclyn A BrennanDepartment of Biomedical Engineering, The George Washington University, Washington, DC, USA.
Katherine GoldrickDepartment of Biomedical Engineering, The George Washington University, Washington, DC, USA.
Igor R EfimovDepartment of Biomedical Engineering, The George Washington University, Washington, DC, USA; Department of Biomedical Engineering, Northwestern University, Chicago, Illinois, USA; Department of Medicine (Cardiology), Northwestern University, Chicago, Illinois, USA. Electronic address: igor.efimov@northwestern.edu.
George Washington University · US

Funding

Comprehensive Structural and Functional Mapping of the Mammalian Cardiac Nervous SystemOT2OD023848 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EFIMOV, IGOR R, FOWLKES, CHARLESS · 2016 to 2021
$21.4M
Graphene optoelectronic biointerfaces for enabling optical cardiac pacemakingR21HL152324 · NHLBI · NORTHWESTERN UNIVERSITY · PI EFIMOV, IGOR R, LU, LUYAO · 2020 to 2021
$440k
IMPLANTABLE MOUSE PACEMAKERR21HL108617 · NHLBI · WASHINGTON UNIVERSITY · PI EFIMOV, IGOR R · 2011 to 2012
$418k
NHLBI NIH HHS R21 HL108617NHLBI NIH HHS R21 HL152324NIH HHS OT2 OD023848
6 · The paper itself

Abstract

backgroundRecently, our laboratory presented functional and molecular evidence for the presence of 2 competing sinoatrial node (SAN) pacemakers in healthy human and rat hearts. Anatomically localized near the superior vena cava and inferior vena cava, the superior and inferior SANs (sSAN and iSAN, respectively) preferentially control fast and slow normal heart rates. However, only 1 dominant pacemaker, primarily the sSAN, was functional in the failing rat heart with hypertrophic cardiomyopathy.

objectivesThis study aimed to determine the transcriptional basis of functional silencing of 1 of 2 dominant pacemakers in failing rat hearts.

methodsAscending aortic constriction was performed on 1-week-old male Sprague-Dawley rat pups to induce left ventricular hypertrophy and heart failure. The dominant pacemaker was anatomically mapped in adult (10-12 weeks old) healthy and failing rat hearts using optical mapping in isolated right atrial tissue preparations. RNA sequencing was used to identify regional sSAN/iSAN gene expression differences between healthy and failing rat hearts.

resultsIn all failing rat hearts optically mapped in this study (n = 4), only the sSAN pacemaker was functional, while the iSAN was silent. Compared to healthy rat hearts, a total of 3,640 genes were downregulated, and 4,518 genes were upregulated in failing rat hearts. The functional quiescence of the iSAN in these failing rat hearts may be explained by their downregulation of sodium, potassium, and calcium ion channels as well as their downregulation of specific structural genes, including ankyrin, titin, and myosin heavy chain. Moreover, the iSAN showed predominant downregulation of several key transcription factors such as Tbx5, Tbx3, Shox2, and Smad9.

conclusionsPressure-overload-induced heart failure resulted in significant downregulation of critical transcription factors, ion channels, and structural transcripts of the iSAN, which could explain the functional silencing of the iSAN in failing rat hearts.

Indexed as

Cardiomyopathy, HypertrophicHeart FailureAnimalsMaleRatsRats, Sprague-DawleySinoatrial NodeTranscription FactorsVena Cava, SuperiorTranscription Factorsarrhythmiasoptical mappingpacemakersinoatrial node

Identifiers

PMID36424000
OpenAlexW4297453825

What OpenQuestion holds

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Registered trials

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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.