The Impact of Liraglutide, a GLP-1 Receptor Agonist, on High Glucose-Induced Inflammation, Apoptosis, Oxidative Stress, and NLRP3 Signaling.

Diabetes-related endothelial dysfunction, alteration in cell signaling, increased oxidative stress and activation of pro-inflammatory processes are the main causes of diabetes-related vascular complications. Glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) play a crucial role in regulating glucose homeostasis, insulin secretion, and reducing inflammation. GLP-1R agonists have been explored for their potential in mitigating diabetes-related vascular dysfunction. The NOD-like receptor protein 3 (NLRP3) inflammasome, a key protein complex in immune response, activates caspase-1 and promotes proinflammatory cytokine secretion. High glucose levels activate NLRP3 in macrophages via reactive oxygen species and mitochondrial dysfunction. This study aims to investigate the effects of GLP-1 receptor agonist, Liraglutide, on cell proliferation, inflammation, oxidative stress and NLRP3-related signaling pathways in human umbilical vein endothelial cells (HUVEC) and human coronary artery endothelial cell (HCAEC) cultures. HUVEC and HCAEC were incubated with Liraglutide (10 and 100 nM, 48 h) either in normoglycemic (5.5 mM) or hyperglycemic (25 mM) condition. Cell proliferation, oxidative stress, mRNA and protein expressions of ASC, caspase-1, NLRP3 which are. components of NLRP3 inflammasome, were determined. Our results showed that, Liraglutide significantly reduced hyperglycemia-induced oxidative stress, mRNA and protein expressions of NLRP3 inflammasome and proinflammatory cytokine levels, as well as cell membrane damage in HUVEC and HCAEC. Our results indicate that Liraglutide may have the potential on preventing hyperglycemia-induced cellular damage by reducing inflammation and immune response activation both in human venous and arterial endothelial cells.