Erk/Hif-1Α/Vegf Pathway: A Molecular Target of Elabela (Ela) Peptide for Attenuating Cardiac Ischemia–Reperfusion Injury in Rats by Promoting Angiogenesis Publisher Pubmed



Rakhshan K¹ ; Sharifi M^{2, 3} ; Ramezani F² ; Azizi Y^{2, 3} ; Aboutaleb N^{2, 3} Show Affiliations
Source: Molecular Biology Reports Published:2022

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. © 2022, The Author(s), under exclusive licence to Springer Nature B.V.