Evidence map›Paper›PMID 26352986›Full record

ArticlePloS one2015

Atrial SERCA2a Overexpression Has No Affect on Cardiac Alternans but Promotes Arrhythmogenic SR Ca2+ Triggers.

Michelle M J Nassal, Xiaoping Wan, Kenneth R Laurita, Michael J Cutler

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

Article in PloS one, 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
0.6field-weighted citation impact, top 28% 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. Article
  2. Role of Reduced Sarco-Endoplasmic Reticulum CaFrontiers in physiology · 2021
    Article
  3. Interleukin-6-Mediated-CaFrontiers in immunology · 2021
    Article
  4. Article
  5. Article
  6. Review
  7. 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

4 authors at 2 institutions in 1 country.

Michelle M J NassalHeart and Vascular Research Center, Case Western Reserve University, Cleveland, OH, United States of America; Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, United States of America.
Xiaoping WanHeart and Vascular Research Center, Case Western Reserve University, Cleveland, OH, United States of America.
Kenneth R LauritaHeart and Vascular Research Center, Case Western Reserve University, Cleveland, OH, United States of America.
Michael J CutlerHeart and Vascular Research Center, Case Western Reserve University, Cleveland, OH, United States of America; Intermountain Heart Institute, Salt Lake City, Utah, United States of America.
Case Western Reserve University · USIntermountain Medical Center · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
Cardiovascular Research Training Program (CRTP)T32HL105338 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI JAIN, MUKESH KUMAR · 2010 to 2014
$1.8M
NCI NIH HHS T32CM007250NHLBI NIH HHS T32 HL105338NHLBI NIH HHS T32HL105338NIGMS NIH HHS T32 GM007250
6 · The paper itself

Abstract

backgroundAtrial fibrillation (AF) is the most common arrhythmia in humans, yet; treatment has remained sub-optimal due to poor understanding of the underlying mechanisms. Cardiac alternans precede AF episodes, suggesting an important arrhythmia substrate. Recently, we demonstrated ventricular SERCA2a overexpression suppresses cardiac alternans and arrhythmias. Therefore, we hypothesized that atrial SERCA2a overexpression will decrease cardiac alternans and arrhythmias.

methodsAdult rat isolated atrial myocytes where divided into three treatment groups 1) Control, 2) SERCA2a overexpression (Ad.SERCA2a) and 3) SERCA2a inhibition (Thapsigargin, 1μm). Intracellular Ca2+ was measured using Indo-1AM and Ca2+ alternans (Ca-ALT) was induced with a standard ramp pacing protocol.

resultsAs predicted, SR Ca2+ reuptake was enhanced with SERCA2a overexpression (p< 0.05) and reduced with SERCA2a inhibition (p<0.05). Surprisingly, there was no difference in susceptibility to Ca-ALT with either SERCA2a overexpression or inhibition when compared to controls (p = 0.73). In contrast, SERCA2a overexpression resulted in increased premature SR Ca2+ (SCR) release compared to control myocytes (28% and 0%, p < 0.05) and concomitant increase in SR Ca2+ load (p<0.05). Based on these observations we tested in-vivo atrial arrhythmia inducibility in control and Ad.SERCA2a animals using an esophageal atrial burst pacing protocol. There were no inducible atrial arrhythmias in Ad.GFP (n = 4) animals though 20% of Ad.SERCA2a (n = 5) animals had inducible atrial arrhythmias (p = 0.20).

conclusionsOur findings suggest that unlike the ventricle, SERCA2a is not a key regulator of cardiac alternans in the atrium. Importantly, SERCA2a overexpression in atrial myocytes can increase SCR, which may be arrhythmogenic.

Indexed as

AnimalsArrhythmias, CardiacAtrial FibrillationBrugada SyndromeCalciumCardiac Conduction System DiseaseGene Expression RegulationGlucansHeart AtriaHeart Conduction SystemHumansMyocytes, CardiacPatch-Clamp TechniquesRatsSarcoplasmic Reticulum Calcium-Transporting ATPasesThapsigarginalternanAtp2a2 protein, ratCalciumGlucansSarcoplasmic Reticulum Calcium-Transporting ATPasesThapsigargin

Identifiers

PMID26352986
PMCPMC4564245
OpenAlexW1764445960

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.