Semaglutide ameliorates coronary microembolization-induced injury by suppressing apoptosis and inflammation via the HMGB1/RAGE/NF-κB p65 pathway
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Hua-Feng Yang1, Hong-Qing Li2, Qiang Wang2
1Cardiac Surgery Intensive Care Unit, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Insights
Semaglutide pretreatment protects against coronary microembolization (CME) by reducing myocardial injury, apoptosis, and inflammation. This effect is mediated through the HMGB1/RAGE/NF-κB p65 signaling pathway, offering a potential therapeutic strategy.
Area of Science:
- Cardiology
- Pharmacology
- Molecular Biology
Background:
- Coronary microembolization (CME) is a primary cause of myocardial injury during cardiac surgery.
- The cardioprotective effects of semaglutide against CME are not well understood.
- This study investigates semaglutide's impact on CME-induced cardiac damage.
Purpose of the Study:
- To evaluate the efficacy of semaglutide in mitigating myocardial injury caused by coronary microembolization.
- To elucidate the underlying molecular mechanisms, including apoptosis and inflammation.
- To explore the role of the HMGB1/RAGE/NF-κB p65 pathway.
Main Methods:
- A rat model of coronary microembolization (CME) was established.
- A H9c2 cardiomyocyte model was induced using lipopolysaccharide and hypoxia.
- Cardiac function, injury markers, cell viability, apoptosis, inflammation, and key signaling molecules (HMGB1, RAGE, NF-κB p65) were assessed following semaglutide or glycyrrhizin treatment.
Main Results:
- Semaglutide pretreatment improved cardiac function and reduced myocardial injury in the CME model.
- Semaglutide significantly attenuated myocardial apoptosis and inflammatory responses both *in vivo* and *in vitro*.
- Semaglutide downregulated HMGB1 expression and inhibited its translocation, impacting the HMGB1/RAGE/NF-κB p65 pathway.
Conclusions:
- Semaglutide pretreatment effectively attenuates myocardial injury induced by CME.
- The cardioprotective effects are achieved by suppressing apoptosis and inflammation.
- These benefits are mediated via the HMGB1/RAGE/NF-κB p65 signaling 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 CME in vivo and in vitro. 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.
