Semaglutide ameliorates coronary microembolization-induced injury by suppressing apoptosis and inflammation via the HMGB1/RAGE/NF-κB p65 pathway.

BACKGROUND: Coronary microembolization (CME) is the major leading cause of perioperative myocardial injury during coronary revascularization. Semaglutide exerts multiple protective biological activities, but its cardioprotective effects on CME remain unclear. Thus, this experiment studied the impact of semaglutide on CME-induced myocardial injury. METHODS: A rat CME model was generated by injecting microspheres into the left ventricle while clamping the ascending aorta. A H9c2 cardiomyocyte model was constructed by stimulation of lipopolysaccharide combined with hypoxia. Semaglutide or the high mobility group box 1 (HMGB1) antagonist glycyrrhizin administrations were ahead of CME and cell modeling. Cardiac function, myocardial injury markers, cell viability and morphological alternations were detected. Apoptotic and inflammatory factors, cytosolic HMGB1 and its translocation, advanced glycosylation end-product specific receptor (RAGE), and nuclear factor kappa B p65 (NF-κB p65) were evaluated. RESULTS: Semaglutide pretreatment ameliorated CME-induced cardiac systolic dysfunction and relieved the cardiac injury. Semaglutide attenuated myocardial apoptosis and inflammatory response following CMEand. Moreover, semaglutide downregulated HMGB1 expression and suppressed its nuclear-cytoplasmic translocation. Both glycyrrhizin and semaglutide administration affected the HMGB1/RAGE/NF-κB p65 pathway after CME. CONCLUSIONS: Semaglutide pretreatment attenuates CME-induced myocardial injury by suppressing apoptosis and inflammation through the HMGB1/RAGE/NF-κB p65 pathway.