Evidence map›Paper›PMID 39328167›Full record

ArticleCirculation research2024

Blunted Cardiac Mitophagy in Response to Metabolic Stress Contributes to HFpEF.

Akira Yoshii, Timothy S McMillen, Yajun Wang, Bo Zhou, Hongye Chen, Durba Banerjee, Melisa Herrero, Pei Wang, Naoto Muraoka, Wang Wang and 2 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
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. An erratum has been issued. Cited by 67 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

67 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  17. Mitophagy in cardiovascular diseases: a literature review.Cardiovascular diagnosis and therapy · 2026
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7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Akira YoshiiDepartment of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center (A.Y., T.S.M., Y.W., B.Z., H.C., D.B., M.H., P.W., W.W., R.T.), University of Washington, Seattle.
Timothy S McMillenDepartment of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center (A.Y., T.S.M., Y.W., B.Z., H.C., D.B., M.H., P.W., W.W., R.T.), University of Washington, Seattle.ORCID 0000-0001-5261-3229
Yajun WangDepartment of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center (A.Y., T.S.M., Y.W., B.Z., H.C., D.B., M.H., P.W., W.W., R.T.), University of Washington, Seattle.ORCID 0009-0003-1774-8744
Bo ZhouDepartment of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center (A.Y., T.S.M., Y.W., B.Z., H.C., D.B., M.H., P.W., W.W., R.T.), University of Washington, Seattle.ORCID 0000-0003-1844-7081
Hongye ChenDepartment of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center (A.Y., T.S.M., Y.W., B.Z., H.C., D.B., M.H., P.W., W.W., R.T.), University of Washington, Seattle.ORCID 0000-0003-1031-1008
Durba BanerjeeDepartment of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center (A.Y., T.S.M., Y.W., B.Z., H.C., D.B., M.H., P.W., W.W., R.T.), University of Washington, Seattle.ORCID 0000-0003-3905-6178
Melisa HerreroDepartment of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center (A.Y., T.S.M., Y.W., B.Z., H.C., D.B., M.H., P.W., W.W., R.T.), University of Washington, Seattle.
Pei WangDepartment of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center (A.Y., T.S.M., Y.W., B.Z., H.C., D.B., M.H., P.W., W.W., R.T.), University of Washington, Seattle.ORCID 0000-0003-0901-2879
Naoto MuraokaInstitute for Stem Cell and Regenerative Medicine (N.M., C.E.M., R.T.), University of Washington, Seattle.ORCID 0000-0003-0057-0292
Wang WangDepartment of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center (A.Y., T.S.M., Y.W., B.Z., H.C., D.B., M.H., P.W., W.W., R.T.), University of Washington, Seattle.ORCID 0000-0001-9093-412X
Charles E MurryInstitute for Stem Cell and Regenerative Medicine (N.M., C.E.M., R.T.), University of Washington, Seattle.ORCID 0000-0003-3862-6773
Rong TianDepartment of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center (A.Y., T.S.M., Y.W., B.Z., H.C., D.B., M.H., P.W., W.W., R.T.), University of Washington, Seattle.ORCID 0000-0002-3676-3830

Funding

Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · PI Sakeneh Zraika · 1986 to 2026
$41.4M
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
Mitochondrial metabolism and macrophage function post MIR01HL149695 · NHLBI · UNIVERSITY OF WASHINGTON · PI TIAN, RONG · 2020 to 2023
$2.9M
Fatty acid oxidation suppresses cardiac hypertrophyR01HL129510 · NHLBI · UNIVERSITY OF WASHINGTON · PI TIAN, RONG · 2015 to 2018
$2.8M
Mitochondrial function and glycolytic switch in pathological cardiac hypertrophyR01HL142628 · NHLBI · UNIVERSITY OF WASHINGTON · PI TIAN, RONG · 2018 to 2021
$2.4M
Regulation and function of mitochondrial calcium uniporter in the heartR56HL153124 · NHLBI · UNIVERSITY OF WASHINGTON · PI WANG, WANG · 2022 to 2022
$736k
NHLBI NIH HHS R01 HL129510NHLBI NIH HHS R01 HL142628NHLBI NIH HHS R01 HL144937NHLBI NIH HHS R01 HL149695NHLBI NIH HHS R56 HL153124NIDDK NIH HHS P30 DK017047
6 · The paper itself

Abstract

backgroundMetabolic remodeling and mitochondrial dysfunction are hallmarks of heart failure with reduced ejection fraction. However, their role in the pathogenesis of HF with preserved ejection fraction (HFpEF) is poorly understood.

methodsIn a mouse model of HFpEF, induced by high-fat diet and Nω-nitrol-arginine methyl ester, cardiac energetics was measured by

resultsHFpEF hearts presented a lower phosphocreatine content and a reduced phosphocreatine/ATP ratio, similar to that in heart failure with reduced ejection fraction. Decreased respiratory function and increased reactive oxygen species production were observed in mitochondria isolated from HFpEF hearts suggesting mitochondrial dysfunction. Cardiac substrate oxidation profile showed a high dependency on fatty acid oxidation in HFpEF hearts, which is the opposite of heart failure with reduced ejection fraction but similar to that in high-fat diet hearts. However, phosphocreatine/ATP ratio and mitochondrial function were sustained in the high-fat diet hearts. We found that mitophagy was activated in the high-fat diet heart but not in HFpEF hearts despite similar extent of obesity suggesting that mitochondrial quality control response was impaired in HFpEF hearts. Using a human induced pluripotent stem cell-derived cardiomyocyte mitophagy reporter, we found that fatty acid loading stimulated mitophagy, which was obliterated by inhibiting fatty acid oxidation. Enhancing fatty acid oxidation by deleting ACC2 (acetyl-CoA carboxylase 2) in the heart stimulated mitophagy and improved HFpEF phenotypes.

conclusionsMaladaptation to metabolic stress in HFpEF hearts impairs mitochondrial quality control and contributed to the pathogenesis, which can be improved by stimulating fatty acid oxidation.

Indexed as

Heart FailureMitochondria, HeartMitophagyMyocytes, CardiacStroke VolumeAnimalsDiet, High-FatDisease Models, AnimalEnergy MetabolismHumansInduced Pluripotent Stem CellsMaleMiceMice, Inbred C57BLStress, Physiologicalfatty acidsheart failuremetabolismmitochondriamitophagy

Identifiers

PMID39328167
PMCPMC11502249

What Socratic 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 Socratic graph.