ERK/HIF-1α/VEGF pathway: a molecular target of ELABELA (ELA) peptide for attenuating cardiac ischemia-reperfusion injury in rats by promoting angiogenesis.
Angiogenesis
ELABELA peptide
Fibrosis
Myocardial ischemia/reperfusion
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Nov 2022
Nov 2022
Historique:
received:
28
06
2022
accepted:
21
07
2022
pubmed:
22
9
2022
medline:
2
11
2022
entrez:
21
9
2022
Statut:
ppublish
Résumé
Myocardial ischemia-reperfusion (I/R) injury is caused by a chain of events such as endothelial dysfunction. This study was conducted to investigate protective effects of ELABELA against myocardial I/R in Wistar rats and clarify its possible mechanisms. METHODS AND RESULTS: MI model was established based on the left anterior descending coronary artery ligation for 30 min. Then, 5 µg/kg of ELA peptide was intraperitoneally infused in rats once per day for 4 days. Western blot assay was used to assay the expression of t-ERK1/2, and p-ERK1/2 in different groups. The amount of myocardial capillary density, the expression levels of VEGF and HIF-1α were evaluated using immunohistochemistry assay. Masson's trichrome staining was utilized to assay cardiac interstitial fibrosis. The results showed that establishment of MI significantly enhanced cardiac interstitial fibrosis and changed p-ERK1/2/ t-ERK1/2 ratio. Likewise, ELA post-treatment markedly increased myocardial capillary density, the expression of several angiogenic factors (VEGF-A, HIF-1α), and reduced cardiac interstitial fibrosis by activation of ERK1/2 signaling pathways. Collectively, ELA peptide has ability to reduce myocardial I/R injury by promoting angiogenesis and reducing cardiac interstitial fibrosis through activating ERK/HIF-1α/VEGF pathway.
Sections du résumé
BACKGROUND
BACKGROUND
Myocardial ischemia-reperfusion (I/R) injury is caused by a chain of events such as endothelial dysfunction. This study was conducted to investigate protective effects of ELABELA against myocardial I/R in Wistar rats and clarify its possible mechanisms. METHODS AND RESULTS: MI model was established based on the left anterior descending coronary artery ligation for 30 min. Then, 5 µg/kg of ELA peptide was intraperitoneally infused in rats once per day for 4 days. Western blot assay was used to assay the expression of t-ERK1/2, and p-ERK1/2 in different groups. The amount of myocardial capillary density, the expression levels of VEGF and HIF-1α were evaluated using immunohistochemistry assay. Masson's trichrome staining was utilized to assay cardiac interstitial fibrosis. The results showed that establishment of MI significantly enhanced cardiac interstitial fibrosis and changed p-ERK1/2/ t-ERK1/2 ratio. Likewise, ELA post-treatment markedly increased myocardial capillary density, the expression of several angiogenic factors (VEGF-A, HIF-1α), and reduced cardiac interstitial fibrosis by activation of ERK1/2 signaling pathways.
CONCLUSION
CONCLUSIONS
Collectively, ELA peptide has ability to reduce myocardial I/R injury by promoting angiogenesis and reducing cardiac interstitial fibrosis through activating ERK/HIF-1α/VEGF pathway.
Identifiants
pubmed: 36129600
doi: 10.1007/s11033-022-07818-y
pii: 10.1007/s11033-022-07818-y
doi:
Substances chimiques
Vascular Endothelial Growth Factor A
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Peptides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
10509-10519Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature B.V.
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