Journal of geriatric cardiology : JGCMar 16, 2026

Semaglutide reduces heart injury from small artery blockages by lowering cell death and inflammation through the HMGB1/RAGE/NF-κB p65 pathway

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Semaglutide pretreatment reduced coronary microembolization-related cardiac injury signals in rat and cardiomyocyte models.

Evidence

This preclinical in vivo rat CME model and in vitro H9c2 cardiomyocyte experiment measured cardiac function, injury markers, apoptosis, inflammation, and HMGB1/RAGE/NF-kB p65 pathway activity.

Caveat

The findings come from pretreatment in animal and cell models, so they do not establish clinical benefit for patients undergoing coronary revascularization.

Simplified

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. in vivo in vitro

CONCLUSIONS: Semaglutide pretreatment attenuates CME-induced myocardial injury by suppressing apoptosis and inflammation through the HMGB1/RAGE/NF-κB p65 pathway.