Growth/differentiation factor 15 (GDF15) expression in the heart after myocardial infarction and cardioprotective effect of pre-ischemic rGDF15 administration.
Growth Differentiation Factor 15
/ metabolism
Animals
Male
Myocardial Infarction
/ metabolism
Rats, Wistar
Rats
Myocardial Reperfusion Injury
/ metabolism
Myocardium
/ metabolism
Cardiotonic Agents
/ pharmacology
Recombinant Proteins
/ administration & dosage
Ischemic Preconditioning, Myocardial
/ methods
Cardioprotection
GDF-15
Heart
Ischemia–reperfusion injury
Preconditioning
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
05 06 2024
05 06 2024
Historique:
received:
17
02
2024
accepted:
03
06
2024
medline:
6
6
2024
pubmed:
6
6
2024
entrez:
5
6
2024
Statut:
epublish
Résumé
Growth/differentiation factor-15 (GDF15) is considered an unfavourable prognostic biomarker for cardiovascular disease in clinical data, while experimental studies suggest it has cardioprotective potential. This study focuses on the direct cardiac effects of GDF15 during ischemia-reperfusion injury in Wistar male rats, employing concentrations relevant to patients at high cardiovascular risk. Initially, we examined circulating levels and heart tissue expression of GDF15 in rats subjected to ischemia-reperfusion and sham operations in vivo. We then evaluated the cardiac effects of GDF15 both in vivo and ex vivo, administering recombinant GDF15 either before 30 min of ischemia (preconditioning) or at the onset of reperfusion (postconditioning). We compared infarct size and cardiac contractile recovery between control and rGDF15-treated rats. Contrary to our expectations, ischemia-reperfusion did not increase GDF15 plasma levels compared to sham-operated rats. However, cardiac protein and mRNA expression increased in the infarcted zone of the ischemic heart after 24 h of reperfusion. Notably, preconditioning with rGDF15 had a cardioprotective effect, reducing infarct size both in vivo (65 ± 5% in control vs. 42 ± 6% in rGDF15 groups) and ex vivo (60 ± 4% in control vs. 45 ± 4% in rGDF15 groups), while enhancing cardiac contractile recovery ex vivo. However, postconditioning with rGDF15 did not alter infarct size or the recovery of contractile parameters in vivo or ex vivo. These novel findings reveal that the short-term exogenous administration of rGDF15 before ischemia, at physiologically relevant levels, protects the heart against ischemia-reperfusion injury in both in vivo and ex vivo settings. The ex vivo results indicate that rGDF15 operates independently of the inflammatory, endocrine and nervous systems, suggesting direct and potent cardioprotective properties against ischemia-reperfusion injury.
Identifiants
pubmed: 38839839
doi: 10.1038/s41598-024-63880-5
pii: 10.1038/s41598-024-63880-5
doi:
Substances chimiques
Growth Differentiation Factor 15
0
Cardiotonic Agents
0
Recombinant Proteins
0
Gdf15 protein, rat
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
12949Subventions
Organisme : Agence Nationale de la Recherche
ID : SMOG15-CE17-009-01
Organisme : Agence Nationale de la Recherche
ID : SMOG15-CE17-009-01
Organisme : Agence Nationale de la Recherche
ID : SMOG15-CE17-009-01
Organisme : Agence Nationale de la Recherche
ID : SMOG15-CE17-009-01
Informations de copyright
© 2024. The Author(s).
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