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- Title
ERK/HIF-1α/VEGF pathway: a molecular target of ELABELA (ELA) peptide for attenuating cardiac ischemia–reperfusion injury in rats by promoting angiogenesis.
- Authors
Rakhshan, Kamran; Sharifi, Masoomeh; Ramezani, Fatemeh; Azizi, Yaser; Aboutaleb, Nahid
- Abstract
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: 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.
- Subjects
PEPTIDES; REPERFUSION injury; DRUG target; HEART injuries; VASCULAR endothelial growth factors; STAINS &; staining (Microscopy)
- Publication
Molecular Biology Reports, 2022, Vol 49, Issue 11, p10509
- ISSN
0301-4851
- Publication type
Article
- DOI
10.1007/s11033-022-07818-y