Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling

• DOI: 10.1016/j.apsb.2024.03.011
• Publication Date: 2024-03-11T01:22:35Z
• Authors: Xuemin He; Siying Wen; Xixiang Tang; Zheyao Wen; Rui Zhang; Shasha Li; Rong Gao; Jin Wang; Yanhua Zhu; Dong Fang; Ting Li; Ruiping Peng; Zhaotian Zhang; Shiyi Wen; Li Zhou; Heying Ai; Yan Lu; Shaochong Zhang; Guojun Shi; Yanming Chen
• Keywords: Sting

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) protect against diabetic cardiovascular diseases and nephropathy. However, their activity in retinopathy (DR) remains unclear. Our retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs controlling DR compared to other glucose-lowering medications, suggesting advantage treatment. By single-cell RNA-sequencing analysis immunostaining, we observed a high expression GLP-1R retinal endothelial cells, which was down-regulated under conditions. Treatment significantly restored the expression, resulting an improvement degeneration, vascular tortuosity, avascular vessels, integrity mice. GO GSEA analyses further implicated enhanced mitochondrial gene translation functions by RAs. Additionally, treatment attenuated STING signaling activation is typically activated leaked DNA. Expression mRNA positively correlated levels angiogenic inflammatory factors cells human fibrovascular membranes. Further investigation that cAMP-responsive element binding protein played role pathway on suppression signaling. This demonstrates novel protection vasculature inhibiting STING-elicited signals.