HMGB1 regulates autophagy via TLR4/NF-κB signaling pathway in myocardial injury induced by coronary microembolization.

Background: Coronary microembolization (CME) is a common and refractory complication of coronary atherosclerotic plaque spontaneous rupture or reperfusion treatment in patients with coronary heart disease, which is closely related to the patient's near-term and long-term prognosis. The specific molecular mechanism of CME leading to myocardial injury is not yet fully understood. This study aims to elucidate the regulatory function of high-mobility group protein box 1 (HMGB1) within the TLR4/NF-κB signaling pathway, and explore the role of autophagy mediated by this signaling pathway in CME-induced myocardial injury.

Methods: A rat model of CME was established by left ventricle injection of microspheres. HMGB1 inhibitor (glycyrrhizin) or autophagy inhibitor (3-methyladenine) was pretreated before CME modeling. Following the animal modeling of CME, we examined alterations in the expression and localization of proteins associated with signaling pathways. Additionally, we monitored the autophagic activity within the myocardium and assessed cardiac function, histological changes in myocardium, and biomarkers indicative of myocardial injury present in serum samples.

Results: In the CME model group, there was a significant upregulation of HMGB1 expression and its migration into the cytoplasm. Concurrently, TLR4 and NF-κB expression levels were elevated, while autophagic activity was diminished. In contrast, when compared to the model group, the glycyrrhizin acid pretreatment group exhibited notable improvements in cardiac dysfunction (LVEF increased by 18.50 ± 1.13%) and myocardial injury (microinfarct size reduced by 19.94 ± 1.07%, P < 0.001). However, this cardioprotective effect was nullified upon pretreatment with the autophagy inhibitor 3-MA.

Conclusion: HMGB1 regulates autophagy through TLR4/NF-κB signaling pathway in CME rat model of myocardial injury induced by coronary microembolization.