Inhibiting STING1 promotes recovery of cardiac function and structure after diabetic myocardial infarction by facilitating angiogenesis.

BACKGROUND AND PURPOSE: Diabetes can lead to serious complications and significantly increase the risk of myocardial infarction. This study aimed to elucidate the role of STING1 in angiogenesis after diabetic myocardial infarction.

METHODS

We established a diabetic myocardial infarction model in wild-type and Sting1-/- mice. Myocardial structure, fibrosis, and cardiac function were assessed via histological analysis and echocardiography. In vitro, primary cardiac microvascular endothelial cells were transfected with siRNA targeting STING1 to evaluate their proliferation, migration, tube formation ability, and apoptosis. Pathway enrichment analysis was performed using Gene Set Enrichment Analysis.

RESULTS

Wild-type diabetic myocardial infarction mice exhibited disordered myocardial structure, increased fibrosis, and impaired cardiac function. In contrast, Sting1-/- mice exhibited restored cardiac function and significantly enhanced angiogenesis. At the cellular level, STING1 inhibition alleviated endothelial cell damage, promoted proliferation, migration, and tube formation, and reduced apoptosis. GSEA further indicated significant enrichment of the Wnt, MAPK, TGF-β, Tight junction, and PI3K-Akt signaling pathways in this process.

CONCLUSION

These findings demonstrate that inhibiting STING1 promotes the recovery of cardiac structure and function after diabetic myocardial infarction by facilitating angiogenesis. This protective effect may involve the regulation of the Wnt, MAPK, TGF-β, Tight junction, and PI3K-Akt signaling pathways.