Ticagrelor Reduces Ischemia-Reperfusion Injury Through the NF-κB-Dependent Pathway in Rats

We recently showed that ticagrelor reduced myocardial ischemia-reperfusion injury (IRI) and downregulated galectin-3 in the ischemic myocardium. This study tested the hypothesis that ticagrelor could reduce IRI through the NF-κB pathway. Rats were randomly divided into sham-operated group, placebo group (gastric administration of saline after IRI), ticagrelor group (gastric administration of ticagrelor after left anterior descending artery ligation), dextran sodium sulfate (DSS) group (DSS was added to drinking water 7 days before IRI), and DSS + ticagrelor group (DSS was added to drinking water 7 days before IRI and gastric administration of ticagrelor after left anterior descending artery ligation). Ticagrelor significantly reduced the infarct size and plasma cTnI at 3 and 7 days after IRI, significantly downregulated protein and mRNA expressions of NF-κB and galectin-3, and mRNA expressions of IL-6 and TNF-α in the ischemic area at 24 hours, 3 and 7 days after IRI. Ticagrelor also significantly decreased plasma high-sensitivity C-reactive protein and NT-proBNP levels at 24 hours and 3 days after IRI. Furthermore, pretreatment with DSS blocked the beneficial effects of ticagrelor. Our study indicates that the cardioprotective effect of ticagrelor might be partly mediated by inhibiting the NF-κB pathway in this rat model of IRI.