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PXD031436-1

PXD031436 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAccumulation of acylcarnitines and mitochondrial dysfunction characterize the loss of neonatal myocardial regeneration capacity
DescriptionMyocardial regeneration capacity declines during the first week after birth and is linked to the adaptation to oxidative metabolism. Utilizing this regenerative window, we characterized the metabolic changes in myocardial injury in 1-day-old regeneration-competent and 7-day-old regeneration-compromised mice. The mice were either sham-operated or received left anterior descending coronary artery ligation, to induce myocardial infarction (MI) and acute ischemic heart failure. Myocardial tissue samples were collected after 21 days for metabolomics, transcriptomics and proteomics analyses. Phenotypic characterizations were carried out using echocardiography, histology as well as mitochondrial structural and functional measurements. By integrating the findings from metabolome and transcriptome examinations, we identified mitochondrial dysfunction at the level of the carnitine shuttle contributing to myocardial regeneration incompetence. Regeneration failure was linked to accumulation of acylcarnitines and insufficient metabolic capacity for fatty acid beta-oxidation. We further identified specific transcription factors and post-transcriptional regulation contributing to both regeneration competence and failure. Rather than shifting from the preferred myocardial oxidative fuel source, our results put forward the facilitation of mitochondrial fatty acid transport and improving the beta- oxidation pathway to overcome the metabolic barriers for repair and regeneration in adult mammals after MI and heart failure.
HostingRepositoryMassIVE
AnnounceDate2023-02-28
AnnouncementXMLSubmission_2023-02-28_01:26:58.846.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMaciej Lalowski
SpeciesList scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationListDeamidated; Oxidation; Carbamidomethyl
InstrumentMALDI Synapt G2-S HDMS
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-02-04 09:43:25ID requested
12023-02-28 01:26:59announced
Publication List
Kankuri E, Finckenberg P, Leinonen J, Tarkia M, Björk S, Purhonen J, Kallijärvi J, Kankainen M, Soliymani R, Lalowski M, Mervaala E. Altered acylcarnitine metabolism and inflexible mitochondrial fuel utilization characterize the loss of neonatal myocardial regeneration capacity. Exp Mol Med (2023), in press.
Keyword List
submitter keyword: heart, myocardial infarction, regeneration, omics analyses, acylcarnitines, fatty acid beta-oxidation
Contact List
Maciej Lalowski
contact affiliationHelsinki Institute for Life Science (HiLIFE) and Faculty of Medicine, Biochemistry/Developmental Biology, Meilahti Clinical Proteomics Core Facility, University of Helsinki, Helsinki, FI-00014
contact emailmaciej.lalowski@helsinki.fi
lab head
Esko Kankuri
contact affiliationUniversity of Helsinki, Medicum, Dept. of Pharmacology
contact emailesko.kankuri@helsinki.fi
lab head
Maciej Lalowski
contact affiliationUniversity of Helsinki/Medicum
contact emailmaciej.lalowski@helsinki.fi
dataset submitter
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Dataset FTP location
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