ERK/HIF-1α/VEGF pathway: a molecular target of ELABELA (ELA) peptide for attenuating cardiac ischemia-reperfusion injury in rats by promoting angiogenesis

Mol Biol Rep. 2022 Nov;49(11):10509-10519. doi: 10.1007/s11033-022-07818-y. Epub 2022 Sep 21.

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.

Keywords: Angiogenesis; ELABELA peptide; Fibrosis; Myocardial ischemia/reperfusion.

MeSH terms

  • Animals
  • Fibrosis
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • MAP Kinase Signaling System
  • Myocardial Reperfusion Injury* / drug therapy
  • Myocardial Reperfusion Injury* / metabolism
  • Neovascularization, Pathologic
  • Peptides / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Vascular Endothelial Growth Factor A* / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Peptides