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

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.

Figure 1

Ratio of infarct area (IA)/area at risk (AAR). Ticagrelor (black circle) significantly reduced IA/AAR ratio at 3 days and 7 days post I/R injury compared to saline‐treated rats (open circle). IA/AAR ratio was also significantly lower at 3 days and 7 days compared to 24 h in ticagrelor group. ** P < 0.01 vs. placebo group. ^# P < 0.05 vs. 24 h, ^## P < 0.01 vs. 24 h

Figure 2

mRNA expression of galectin‐3 (A), TNF‐ α (B) and IL‐6 (C) in the myocardial tissue of sham group (white bar), placebo group (gray bar) and ticagrelor group (black bar) in infarct area at 24 h, 3 days and 7 days post I/R. * P < 0.05 vs. sham‐operated group; ^† P < 0.05 vs. placebo group at the same time point; ^‡ P < 0.05 vs. 24‐h group within the same treatment group

Figure 3

(A) S1, S3 and S7 represents sham group at 24 h, 3 days and 7 days; P1, P3, P7 represents placebo group at 24 h, 3 days and 7 days; T1, T3, T7 represents ticagrelor group at 24 h, 3 days and 7 days. Representative blot for galectin‐3 of various groups at 24 h, 3 days and 7 days post sham operation or I/R injury. Protein expression of galectin‐3 (B) in the myocardial tissue of sham group (white bar) and infarct area of placebo group (gray bar) and ticagrelor group (black bar) at 24 h, 3 days and 7 days post I/R injury. * P < 0.05 vs. sham‐operated group; ^† P < 0.05 vs. placebo group at the same time point; ^‡ P < 0.05 vs. 24‐h group within the same treatment group