Esomeprazole inhibits endoplasmic reticulum stress and ameliorates myocardial ischemia-reperfusion injury

Biochem Biophys Res Commun. 2022 Oct 30:627:84-90. doi: 10.1016/j.bbrc.2022.08.013. Epub 2022 Aug 13.

Abstract

Proton pump inhibitors (PPIs) are often prescribed in association with clopidogrel and aspirin to patients with myocardial infraction (MI), but their effects on heart is controversial. The purpose of this study was to investigate the effects and potential mechanism of omeprazole (OME) and esomeprazole (ESO) in myocardial ischemia reperfusion (I/R) injury. In the present study, mice were treated with OME, ESO or vehicle for 3 weeks and then subjected to myocardial I/R or sham surgery. At 1 day after surgery, echocardiography was performed to access cardiac injury. Hematoxylin and eosin (H&E) staining was performed to evaluate cardiomyocyte morphology. The IL1β was evaluated by Immunohistochemistry (IHC). Elisa was used to detect cTnt content in serum. The expression of CD86, CD206, CHOP, ATF6, eIF2α and p eIF2α were determined by Western blot (WB). The result showed that ESO markedly improved the left ventricular ejection fraction (LVEF), shortening fraction (FS), suppressed inflammatory infiltration, endoplasmic reticulum stress (ERS) and decreased proinflammatory macrophages in I/R hearts, while OME had no significant effects on cardiac function, inflammation and ERS in the I/R heart. In conclusion, ESO but not OME pretreatment reduces the proportion of proinflammatory macrophages, inhibits endoplasmic reticulum stress, and alleviates I/R injury in mice, indicating that ESO maybe a more proper PPI than OME for application in I/R injury.

Keywords: Endoplasmic reticulum stress; Inflammation; Ischemia reperfusion (I/R) injury; Proton pump inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Endoplasmic Reticulum Stress
  • Esomeprazole / pharmacology
  • Esomeprazole / therapeutic use
  • Mice
  • Myocardial Reperfusion Injury* / drug therapy
  • Myocardial Reperfusion Injury* / metabolism
  • Myocytes, Cardiac / metabolism
  • Reperfusion Injury*
  • Stroke Volume
  • Ventricular Function, Left

Substances

  • Esomeprazole