Evidence map›Paper›PMID 36470336›Full record

ArticleJournal of molecular and cellular cardiology2023

dATP elevation induces myocardial metabolic remodeling to support improved cardiac function.

Ketaki N Mhatre, Jason D Murray, Galina Flint, Timothy S McMillen, Gerhard Weber, Majid Shakeri, An-Yue Tu, Sonette Steczina, Robert Weiss, David J Marcinek and 5 more

RetractedOpen access · greenAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of molecular and cellular cardiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Ketaki N MhatreDepartment of Bioengineering, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
Jason D MurrayDepartment of Bioengineering, University of Washington, Seattle, WA 98109, USA; Department of Physiology and Biophysics, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
Galina FlintDepartment of Bioengineering, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
Timothy S McMillenDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98109, USA; Center for Translational Muscle Research, University of Washington, Seattle, WA 98109, USA.
Gerhard WeberDivision of Cardiology, University of Washington, Seattle, WA 98109, USA.
Majid ShakeriDivision of Cardiology, University of Washington, Seattle, WA 98109, USA.
An-Yue TuDepartment of Bioengineering, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
Sonette SteczinaDepartment of Bioengineering, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
Robert WeissDepartment of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.
David J MarcinekDepartment of Radiology, University of Washington, Seattle, WA, USA.
Charles E MurryDivision of Cardiology, University of Washington, Seattle, WA 98109, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
Daniel RafteryDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98109, USA; The Mitochondria and Metabolism Center (MMC), University of Washington, Seattle, WA 98109, USA; Center for Translational Muscle Research, University of Washington, Seattle, WA 98109, USA.
Rong TianDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98109, USA; The Mitochondria and Metabolism Center (MMC), University of Washington, Seattle, WA 98109, USA; Center for Translational Muscle Research, University of Washington, Seattle, WA 98109, USA.
Farid Moussavi-HaramiDivision of Cardiology, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA; Center for Translational Muscle Research, University of Washington, Seattle, WA 98109, USA. Electronic address: moussavi@uw.edu.
Michael RegnierDepartment of Bioengineering, University of Washington, Seattle, WA 98109, USA; Department of Physiology and Biophysics, University of Washington, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA; Center for Translational Muscle Research, University of Washington, Seattle, WA 98109, USA. Electronic address: mregnier@uw.edu.
University of Washington · USCornell University · US

Funding

SPECIFICITY OF OXYGEN DNA DAMAGE AND MUTAGENESISP01AG001751 · NIA · UNIVERSITY OF WASHINGTON · PI PRUSKY, GLEN THOMAS · 1985 to 2021
$29.6M
Wellstone Muscular Dystrophy Specialized Research Center (Seattle)P50AR065139 · NIAMS · UNIVERSITY OF WASHINGTON · PI MICHAEL REGNIER · 2018 to 2026
$15.9M
From proteins to cells to tissues: A multi-scale assessment of biomechanical regulation by the myosin molecular motorRM1GM131981 · NIGMS · STANFORD UNIVERSITY · PI BERNSTEIN, DANIEL, MACK, DAVID LEE · 2019 to 2023
$10.3M
Mechanisms of Brain Dysmorphology in MN1 C-Terminal Truncation Syndrome, a Novel Intellectual Developmental Disability Disorder P50HD103524 · NICHD · UNIVERSITY OF WASHINGTON · PI Sandra E Juul · 2020 to 2026
$9.9M
UW Center for Translational Muscle Research (Overall Application)P30AR074990 · NIAMS · UNIVERSITY OF WASHINGTON · PI Jennifer Michelle Davis, DANIEL RAFTERY · 2019 to 2026
$7.5M
Engineered Stem Cells for Cardiac RepairR01HL128368 · NHLBI · UNIVERSITY OF WASHINGTON · PI REGNIER, MICHAEL · 2018 to 2025
$6.1M
NAD+/NADH ratio, protein acetylation and mitochondrial functionR01HL110349 · NHLBI · UNIVERSITY OF WASHINGTON · PI TIAN, RONG · 2011 to 2020
$5.7M
Mechanistic Studies of NAD+/NADH in Human Heart FailureR01HL144937 · NHLBI · UNIVERSITY OF WASHINGTON · PI O'BRIEN, KEVIN D., TIAN, RONG · 2019 to 2023
$4.2M
Experimental and Computational Studies in Genetic CardiomyopathiesR01HL157169 · NHLBI · UNIVERSITY OF WASHINGTON · PI Farid Moussavi-Harami · 2022 to 2026
$3.3M
Effect of elevated dATP on contractile function and the Frank-Starling relationship in models of dilated cardiomyopathyK08HL128826 · NHLBI · UNIVERSITY OF WASHINGTON · PI MOUSSAVI-HARAMI, FARID · 2016 to 2021
$851k
NHLBI NIH HHS K08 HL128826NHLBI NIH HHS R01 HL110349NHLBI NIH HHS R01 HL128368NHLBI NIH HHS R01 HL144937NHLBI NIH HHS R01 HL157169NIAMS NIH HHS P30 AR074990NIA NIH HHS P01 AG001751NICHD NIH HHS P50 HD103524NIGMS NIH HHS RM1 GM131981
6 · The paper itself

Abstract

Hallmark features of systolic heart failure are reduced contractility and impaired metabolic flexibility of the myocardium. Cardiomyocytes (CMs) with elevated deoxy ATP (dATP) via overexpression of ribonucleotide reductase (RNR) enzyme robustly improve contractility. However, the effect of dATP elevation on cardiac metabolism is unknown. Here, we developed proteolysis-resistant versions of RNR and demonstrate that elevation of dATP/ATP to ∼1% in CMs in a transgenic mouse (TgRRB) resulted in robust improvement of cardiac function. Pharmacological approaches showed that CMs with elevated dATP have greater basal respiratory rates by shifting myosin states to more active forms, independent of its isoform, in relaxed CMs. Targeted metabolomic profiling revealed a significant reprogramming towards oxidative phosphorylation in TgRRB-CMs. Higher cristae density and activity in the mitochondria of TgRRB-CMs improved respiratory capacity. Our results revealed a critical property of dATP to modulate myosin states to enhance contractility and induce metabolic flexibility to support improved function in CMs.

Indexed as

MyocardiumRibonucleotide ReductasesAdenosine TriphosphateAnimalsMiceMice, TransgenicMyocardial ContractionMyocytes, CardiacMyosinsAdenosine TriphosphateMyosinsRibonucleotide ReductasesCardiomyocyte metabolismContractiondATPDRXMitochondrial remodelingmyosin activator

Identifiers

PMID36470336
PMCPMC9974746
OpenAlexW4311753755

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.