Evidence map›Paper›PMID 34139234›Full record

ArticleJournal of molecular and cellular cardiology2021

Serum response factor deletion 5 regulates phospholamban phosphorylation and calcium uptake.

Kathleen C Woulfe, Danielle A Jeffrey, Julie Pires Da Silva, Cortney E Wilson, Jennifer H Mahaffey, Edward Lau, Dobromir Slavov, Frehiwet Hailu, Anis Karimpour-Fard, Karen Dockstader and 4 more

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular and cellular cardiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 40% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. 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 3 institutions in 1 country.

Kathleen C WoulfeDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Danielle A JeffreyDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Julie Pires Da SilvaDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Cortney E WilsonDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Jennifer H MahaffeyDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Edward LauDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Dobromir SlavovDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Frehiwet HailuDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Anis Karimpour-FardDepartment of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Karen DockstaderDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Michael R BristowDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Brian L StaufferDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States; Denver Health Medical Center, Denver, CO, United States.
Shelley D MiyamotoDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Children's Hospital of Colorado, Aurora, CO, United States.
Carmen C SucharovDepartment of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States. Electronic address: kika.sucharov@cuanschutz.edu.
University of Colorado Anschutz Medical Campus · USChildren's Hospital Colorado · USUniversity of Colorado Denver · US

Funding

NIH Prior Approval Process ProfessionalUL1TR002535 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2018 to 2022
$51.1M
Suppression of ERalpha in Hematopoietic Stem Cell-Derived Adipocytes Increases Adiposity via Kynurenine and the Aryl Hydrocarbon ReceptorU54AG062319 · NIA · UNIVERSITY OF COLORADO DENVER · PI Wendy M Kohrt · 2018 to 2026
$13.5M
UCHSC: Building Interdisciplinary Research Careers in Women's HealthK12HD057022 · NICHD · UNIVERSITY OF COLORADO DENVER · PI REGENSTEINER, JUDITH G., SANTORO, NANETTE F. · 2007 to 2023
$8.5M
PREDOCTORAL TRAINING PROGRAM IN PHARMACOLOGYT32GM007635 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI DELL'ACQUA, MARK L · 1985 to 2023
$6.1M
Molecular and Functional Mechanisms of Pediatric Heart FailureR01HL107715 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI STAUFFER, BRIAN L · 2012 to 2016
$2.8M
The Colorado Building Interdisciplinary Research Careers in Women's Health ProgramK12AR084226 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI JUDITH G. REGENSTEINER, Nanette F. Santoro · 2023 to 2026
$2.5M
Investigations of Pathologic Remodeling Using Pediatric Heart Failure SerumK24HL150630 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI SUCHAROV, CARMEN C · 2020 to 2024
$537k
Sex-specific regulation of myofibrillar function in the aging heartK01AG066845 · NIA · UNIVERSITY OF COLORADO DENVER · PI WOULFE, KATHLEEN · 2020 to 2023
$467k
NCATS NIH HHS UL1 TR002535NHLBI NIH HHS K24 HL150630NHLBI NIH HHS R01 HL107715NIAMS NIH HHS K12 AR084226NIA NIH HHS K01 AG066845NIA NIH HHS U54 AG062319NICHD NIH HHS K12 HD057022NIGMS NIH HHS T32 GM007635
6 · The paper itself

Abstract

aimsPediatric dilated cardiomyopathy (pDCM) is characterized by unique age-dependent molecular mechanisms that include myocellular responses to therapy. We previously showed that pDCM, but not adult DCM patients respond to phosphodiesterase 3 inhibitors (PDE3i) by increasing levels of the second messenger cAMP and consequent phosphorylation of phospholamban (PLN). However, the molecular mechanisms involved in the differential pediatric and adult response to PDE3i are not clear. METHODS AND

resultsQuantification of serum response factor (SRF) isoforms from the left ventricle of explanted hearts showed that PDE3i treatment affects expression of SRF isoforms in pDCM hearts. An SRF isoform lacking exon 5 (SRFdel5) was highly expressed in the hearts of pediatric, but not adult DCM patients treated with PDE3i. To determine the functional consequence of expression of SRFdel5, we overexpressed full length SRF or SRFdel5 in cultured cardiomyocytes with and without adrenergic stimulation. Compared to a control adenovirus, expression of SRFdel5 increased phosphorylation of PLN, negatively affected expression of the phosphatase that promotes dephosphorylation of PLN (PP2Cε), and promoted faster calcium reuptake, whereas expression of full length SRF attenuated calcium reuptake through blunted phosphorylation of PLN.

conclusionsTaken together, these data indicate that expression of SRFdel5 in pDCM hearts in response to PDE3i contributes to improved function through regulating PLN phosphorylation and thereby calcium reuptake.

Indexed as

AnimalsCalciumCalcium-Binding ProteinsCardiomyopathy, DilatedCell LineFemaleHeart VentriclesHEK293 CellsHumansMyocytes, CardiacPhospholambanPhosphorylationRatsRats, Sprague-DawleySarcoplasmic Reticulum Calcium-Transporting ATPasesSerum Response FactorCalciumCalcium-Binding ProteinsPhospholambanSarcoplasmic Reticulum Calcium-Transporting ATPasesSerum Response FactorCalcium reuptakePediatric dilated cardiomyopathyPhosphodiesterase 3 inhibitionPhospholambanSerum response factor

Identifiers

PMID34139234
PMCPMC8546760
OpenAlexW3171174501

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.