Evidence map›Paper›PMID 38095088›Full record

ArticleCirculation research2024

Troponin I Tyrosine Phosphorylation Beneficially Accelerates Diastolic Function.

Lorien G Salyer, Hussam E Salhi, Elizabeth A Brundage, Vikram Shettigar, Sarah L Sturgill, Helena Zanella, Benjamin Templeton, Eaman Abay, Kathryn M Emmer, Jeovanna Lowe and 7 more

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In one paragraph

Article in Circulation research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.3field-weighted citation impact, top 17% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Novel Drug Targets in Diastolic Heart Disease.International journal of molecular sciences · 2025
    Review
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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

17 authors at 4 institutions in 1 country.

Lorien G SalyerDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute (L.G.S., H.E.S., E.A.B., V.S., S.L.S., H.Z., B.T., E.A., J.L., J.A.R.-F., M.T.Z., B.J.B.), Ohio State University, Columbus.
Hussam E SalhiDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute (L.G.S., H.E.S., E.A.B., V.S., S.L.S., H.Z., B.T., E.A., J.L., J.A.R.-F., M.T.Z., B.J.B.), Ohio State University, Columbus.
Elizabeth A BrundageDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute (L.G.S., H.E.S., E.A.B., V.S., S.L.S., H.Z., B.T., E.A., J.L., J.A.R.-F., M.T.Z., B.J.B.), Ohio State University, Columbus.ORCID 0000-0002-7523-6670
Vikram ShettigarDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute (L.G.S., H.E.S., E.A.B., V.S., S.L.S., H.Z., B.T., E.A., J.L., J.A.R.-F., M.T.Z., B.J.B.), Ohio State University, Columbus.
Sarah L SturgillDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute (L.G.S., H.E.S., E.A.B., V.S., S.L.S., H.Z., B.T., E.A., J.L., J.A.R.-F., M.T.Z., B.J.B.), Ohio State University, Columbus.
Helena ZanellaDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute (L.G.S., H.E.S., E.A.B., V.S., S.L.S., H.Z., B.T., E.A., J.L., J.A.R.-F., M.T.Z., B.J.B.), Ohio State University, Columbus.
Benjamin TempletonDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute (L.G.S., H.E.S., E.A.B., V.S., S.L.S., H.Z., B.T., E.A., J.L., J.A.R.-F., M.T.Z., B.J.B.), Ohio State University, Columbus.
Eaman AbayDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute (L.G.S., H.E.S., E.A.B., V.S., S.L.S., H.Z., B.T., E.A., J.L., J.A.R.-F., M.T.Z., B.J.B.), Ohio State University, Columbus.
Kathryn M EmmerUniversity Laboratory Animal Resources (K.M.E.), Ohio State University, Columbus.
Jeovanna LoweDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute (L.G.S., H.E.S., E.A.B., V.S., S.L.S., H.Z., B.T., E.A., J.L., J.A.R.-F., M.T.Z., B.J.B.), Ohio State University, Columbus.ORCID 0009-0001-5779-0192
Jill A Rafael-FortneyDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute (L.G.S., H.E.S., E.A.B., V.S., S.L.S., H.Z., B.T., E.A., J.L., J.A.R.-F., M.T.Z., B.J.B.), Ohio State University, Columbus.ORCID 0000-0002-3239-8530
Narasimham ParinandiDivision of Pulmonary, Critical Care and Sleep Medicine (N.P.), Ohio State University, Columbus.ORCID 0000-0003-3489-0286
D Brian FosterDivision of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (D.B.F.).ORCID 0000-0002-9290-9590
Timothy A McKinseyDepartment of Medicine, Division of Cardiology (T.A.M., K.C.W.), University of Colorado Anschutz Medical Campus, Aurora.ORCID 0000-0001-7778-4470
Kathleen C WoulfeDepartment of Medicine, Division of Cardiology (T.A.M., K.C.W.), University of Colorado Anschutz Medical Campus, Aurora.ORCID 0000-0001-9885-7026
Mark T ZioloDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute (L.G.S., H.E.S., E.A.B., V.S., S.L.S., H.Z., B.T., E.A., J.L., J.A.R.-F., M.T.Z., B.J.B.), Ohio State University, Columbus.ORCID 0000-0002-8810-2284
Brandon J BiesiadeckiDepartment of Physiology and Cell Biology, Davis Heart and Lung Research Institute (L.G.S., H.E.S., E.A.B., V.S., S.L.S., H.Z., B.T., E.A., J.L., J.A.R.-F., M.T.Z., B.J.B.), Ohio State University, Columbus.
Anna Needs Neuroblastoma Answers · USThe Ohio State University · USUniversity of Colorado Anschutz Medical Campus · USJohns Hopkins University · US

Funding

Regulation of Chromatin Signaling in Heart Failure by the BRD4 Bromodomain Protein.R01HL127240 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI MCKINSEY, TIMOTHY, SRIVASTAVA, DEEPAK · 2015 to 2022
$6.4M
Integrated Crosstalk of Thin Filament Post-translational ModificationsR01HL114940 · NHLBI · OHIO STATE UNIVERSITY · PI BIESIADECKI, BRANDON J · 2013 to 2021
$3.6M
Deacetylase-Dependent Control of Diastolic Dysfunction and HFpEFR01HL147558 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI HOUSER, STEVEN R, MCKINSEY, TIMOTHY · 2019 to 2022
$3.1M
Regulation of Cardiac Signaling by Class I Histone DeacetylasesR01HL116848 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI MCKINSEY, TIMOTHY · 2013 to 2021
$3.1M
BAT as a therapeutic for the metabolic and cardiac dysfunction with senescence.R01AG060542 · NIA · OHIO STATE UNIVERSITY · PI COEN, PAUL MARTIN, STANFORD, KRISTIN I · 2019 to 2023
$3.0M
Small molecule therapies targeting chromatin architecture in heart failureR01HL150225 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MCKINSEY, TIMOTHY, VONDRISKA, THOMAS M. · 2020 to 2023
$2.9M
Retinoid Metabolism in the Adult Heart and Heart FailureR01HL164478 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI D Brian Foster, MAUREEN A KANE · 2023 to 2026
$2.8M
Troponin I phosphorylation as a novel novel cardiac inotropeR01HL164795 · NHLBI · OHIO STATE UNIVERSITY · PI Brandon J Biesiadecki · 2023 to 2026
$2.6M
Training To Provide the Knowledge, Skills, and Culture To the Next Generation of Cardiovascular ScientistsT32HL134616 · NHLBI · OHIO STATE UNIVERSITY · PI Brandon J Biesiadecki, Jill A Rafael-Fortney · 2017 to 2026
$2.6M
Mechanisms of mineralocorticoid receptor antagonism on inflammation in muscular dystrophyR01NS124681 · NINDS · OHIO STATE UNIVERSITY · PI Jill A Rafael-Fortney · 2022 to 2026
$2.1M
Screening and Development of Small Molecule HDAC11 Inhibitors to Treat Obesity and Diabetes.R01DK119594 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI LIN, HENING, MCKINSEY, TIMOTHY · 2019 to 2022
$2.1M
Sex-specific regulation of myofibrillar function in the aging heartK01AG066845 · NIA · UNIVERSITY OF COLORADO DENVER · PI WOULFE, KATHLEEN · 2020 to 2023
$467k
NHLBI NIH HHS F31 HL168877NHLBI NIH HHS R01 HL114940NHLBI NIH HHS R01 HL116848NHLBI NIH HHS R01 HL127240NHLBI NIH HHS R01 HL147558NHLBI NIH HHS R01 HL150225NHLBI NIH HHS R01 HL164478NHLBI NIH HHS R01 HL164795NHLBI NIH HHS R43 HL154959NHLBI NIH HHS T32 HL134616NIA NIH HHS K01 AG066845NIA NIH HHS R01 AG060542NIA NIH HHS R56 AG060542NIDDK NIH HHS R01 DK119594NINDS NIH HHS R01 NS124681
6 · The paper itself

Abstract

backgroundA healthy heart is able to modify its function and increase relaxation through post-translational modifications of myofilament proteins. While there are known examples of serine/threonine kinases directly phosphorylating myofilament proteins to modify heart function, the roles of tyrosine (Y) phosphorylation to directly modify heart function have not been demonstrated. The myofilament protein TnI (troponin I) is the inhibitory subunit of the troponin complex and is a key regulator of cardiac contraction and relaxation. We previously demonstrated that TnI-Y26 phosphorylation decreases calcium-sensitive force development and accelerates calcium dissociation, suggesting a novel role for tyrosine kinase-mediated TnI-Y26 phosphorylation to regulate cardiac relaxation. Therefore, we hypothesize that increasing TnI-Y26 phosphorylation will increase cardiac relaxation in vivo and be beneficial during pathological diastolic dysfunction.

methodsThe signaling pathway involved in TnI-Y26 phosphorylation was predicted in silico and validated by tyrosine kinase activation and inhibition in primary adult murine cardiomyocytes. To investigate how TnI-Y26 phosphorylation affects cardiac muscle, structure, and function in vivo, we developed a novel TnI-Y26 phosphorylation-mimetic mouse that was subjected to echocardiography, pressure-volume loop hemodynamics, and myofibril mechanical studies. TnI-Y26 phosphorylation-mimetic mice were further subjected to the nephrectomy/DOCA (deoxycorticosterone acetate) model of diastolic dysfunction to investigate the effects of increased TnI-Y26 phosphorylation in disease.

resultsSrc tyrosine kinase is sufficient to phosphorylate TnI-Y26 in cardiomyocytes. TnI-Y26 phosphorylation accelerates in vivo relaxation without detrimental structural or systolic impairment. In a mouse model of diastolic dysfunction, TnI-Y26 phosphorylation is beneficial and protects against the development of disease.

conclusionsWe have demonstrated that tyrosine kinase phosphorylation of TnI is a novel mechanism to directly and beneficially accelerate myocardial relaxation in vivo.

Indexed as

CalciumTroponin IAnimalsMiceMyocardial ContractionMyofibrilsPhosphorylationProtein Processing, Post-TranslationalProtein-Tyrosine KinasesTyrosineCalciumProtein-Tyrosine KinasesTroponin ITyrosinehemodynamicsmyofibrilsphosphorylationtroponin Ityrosine

Identifiers

PMID38095088
PMCPMC10872382
OpenAlexW4389742574

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.