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

Abstract

AimsThe 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.MethodsWe 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.ResultsOur 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.ConclusionsOur 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.

Galectin-3 in Cardiovascular Diseases

“…The role of Gal-3 in fibroblast activation involves up-regulation of the cytoskeletal proteins, the synthesis of new matrix components such as type I collagen and the inhibition of extracellular matrix component degradation down-regulating matrix metalloproteinases [78]. Moreover, another study showed that Gal-3 infusion caused myocardial fibrosis, which was neutralized by an anti-fibrotic agent, suggesting that Gal-3 may be involved in the development and resolution of fibrosis [81].…”

Ticagrelor Improves Remodeling, Reduces Apoptosis, Inflammation and Fibrosis and Increases the Number of Progenitor Stem Cells After Myocardial Infarction in a Rat Model of Ischemia Reperfusion

“…Therefore, the observed improved heart function may rather be related to effects on inflammation, apoptosis and remodeling post infarction. Also, others have shown that the cardioprotective effect of ticagrelor has long-term positive effects on heart function in rat [7] and pig [8] ischemia reperfusion models. In the rat, ticagrelor treatment started after coronary artery ligation and continued after infarction, reduced IS and downregulated mRNA and protein expression of galectin-3, as well as mRNA expression of TNF-α and IL-6 in the infarct area at 24 h, 3 and 7 days post infarction [7].…”

“…Also, others have shown that the cardioprotective effect of ticagrelor has long-term positive effects on heart function in rat [7] and pig [8] ischemia reperfusion models. In the rat, ticagrelor treatment started after coronary artery ligation and continued after infarction, reduced IS and downregulated mRNA and protein expression of galectin-3, as well as mRNA expression of TNF-α and IL-6 in the infarct area at 24 h, 3 and 7 days post infarction [7]. In the pig, ticagrelor, but not clopidogrel, started before infarction and continued for 42 days thereafter, reduced myocardial IS and improved long-term remodeling [8].…”

P2Y12-dependent activation of hematopoietic stem and progenitor cells promotes emergency hematopoiesis after myocardial infarction

“…For P2Y 12 antagonist treatment, we chose the second generation thienopyridine prasugrel, which was reported to be more potent than clopidogrel in terms of more rapid and consistent P2Y 12 inhibition [ 75 ]. Despite its promising favorable effects on infarct size, cytokine release and cardiac remodeling [ 38 , 69 , 72 ] the competitive P2Y 12 inhibitor ticagrelor was not used due to known pleiotropic effects beyond P2Y 12 receptor inhibition, i.e. inhibition of toll like receptors-1/2 (TLR1/2), the protease activated receptor (PAR)-pathway [ 71 ] and the equilibrative nucleoside transporter 1 (ENT1), which increases extracellular concentrations of adenosine [ 2 ].…”