Ticagrelor attenuates myocardial ischaemia-reperfusion injury possibly through downregulating galectin-3 expression in the infarct area of rats

Br J Clin Pharmacol. 2018 Jun;84(6):1180-1186. doi: 10.1111/bcp.13536. Epub 2018 Mar 9.

Abstract

Aims: The full benefits of myocardial revascularization strategies applied to acute myocardial infarction patients might be reduced by myocardial ischaemia and reperfusion (I/R) injury. It is known that inflammation plays an important role in the pathogenesis of I/R injury and galectin-3, a known inflammatory factor, is actively involved in ischaemia-induced inflammation and fibrosis of various organs. Previous studies demonstrated that anti-platelets therapy with ticagrelor, a new P2Y12 receptor antagonist, could effectively attenuate myocardial I/R injury and I/R injury-related inflammatory responses. It remains unknown whether the cardioprotective effects of ticagrelor are also mediated by modulating myocardial galectin-3 expression.

Methods: We determined the ratio of infarct area (IA)/area at risk (AAR), expression of galectin-3, TNF-α and IL-6 in infarct area of rats treated with placebo (equal volume saline per gastric gavage immediately after LAD ligation, then once daily till study end) or ticagrelor (150 mg kg-1 dissolved in saline per gastric gavage immediately after LAD ligation, then once daily till study end) at 24 h, 3 and 7 days post I (45 min)/R injury. Sham-operated rats served as control.

Results: Our results showed that ticagrelor treatment significantly reduced IA/AAR ratio at 3 and 7 days post I/R, downregulated mRNA and protein expression of galectin-3, as well as mRNA expression of TNF-α and IL-6 in infarct area at 24 h, 3 and 7 days post I/R.

Conclusions: Our results suggest that the cardioprotective effects of ticagrelor might partly be mediated by downregulating galectin-3 expression in infarct area in this rat model of myocardial I/R injury.

Keywords: galectin-3; inflammation; ischaemia-reperfusion injury; ticagrelor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cytoprotection
  • Disease Models, Animal
  • Down-Regulation
  • Galectin 3 / genetics
  • Galectin 3 / metabolism*
  • Inflammation Mediators / metabolism*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / prevention & control*
  • Myocardial Reperfusion Injury / genetics
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Rats, Sprague-Dawley
  • Ticagrelor / pharmacology*
  • Time Factors
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Galectin 3
  • Il6 protein, rat
  • Inflammation Mediators
  • Interleukin-6
  • Lgals3 protein, rat
  • Tumor Necrosis Factor-alpha
  • Ticagrelor