PXD031436-1

PXD031436 is an original dataset announced via ProteomeXchange.

Title	Accumulation of acylcarnitines and mitochondrial dysfunction characterize the loss of neonatal myocardial regeneration capacity
Description	Myocardial 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.
HostingRepository	MassIVE
AnnounceDate	2023-02-28
AnnouncementXML	Submission_2023-02-28_01:26:58.846.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maciej Lalowski
SpeciesList	scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationList	Deamidated; Oxidation; Carbamidomethyl
Instrument	MALDI Synapt G2-S HDMS

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-04 09:43:25	ID requested
⏵ 1	2023-02-28 01:26:59	announced

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.

submitter keyword: heart, myocardial infarction, regeneration, omics analyses, acylcarnitines, fatty acid beta-oxidation

Maciej Lalowski
contact affiliation	Helsinki Institute for Life Science (HiLIFE) and Faculty of Medicine, Biochemistry/Developmental Biology, Meilahti Clinical Proteomics Core Facility, University of Helsinki, Helsinki, FI-00014
contact email	maciej.lalowski@helsinki.fi
lab head
Esko Kankuri
contact affiliation	University of Helsinki, Medicum, Dept. of Pharmacology
contact email	esko.kankuri@helsinki.fi
lab head
Maciej Lalowski
contact affiliation	University of Helsinki/Medicum
contact email	maciej.lalowski@helsinki.fi
dataset submitter

MassIVE dataset URI

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