Endocrine Abstracts

JOINT1672

Atherosclerosis is a chronic cardiovascular condition characterized by the accumulation of oxidized low-density lipoprotein (ox-LDL) and the aggregation of vascular cells, leading to endothelial dysfunction and plaque formation. This study investigates the potential anti-atherogenic properties of Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 inhibitor (SGLT2i) primarily used in managing type 2 diabetes (T2D). Recent clinical trials have highlighted DAPA’s cardiovascular benefits, particularly in reducing heart failure and cardiovascular mortality, suggesting a broader therapeutic role beyond glucose regulation. In this study, we aim to explore the protective mechanism of DAPA in oxLDL-caused endothelial damage. The 150 μg/ml oxLDL dosage was stimulated to human umbilical vein endothelial cells (HUVECs) for 24 h with or without DAPA co-treatment. We found that DAPA increased the phosphorylation of AMPK in a dosage-dependent and time-dependent manner. DAPA reversed oxLDL-impaired cell viability by MTT assay. However, silencing AMPK by siRNA obliterates this finding. DAPA reduced oxidative stress markers, such as superoxide and hydrogen peroxide production, under oxLDL stimulation. This reduction is regulated by AMPK-mediated NADPH oxidase activity and enhances the antioxidant defense system. We also found that DAPA mitigates oxLDL-induced apoptosis in endothelial cells by reducing intracellular calcium levels, stabilizing mitochondrial membrane potential, and modulating the expression of pro-apoptotic and anti-apoptotic proteins. Silencing AMPK by siRNA obliterates this finding. Together, those results contribute to developing novel therapeutic strategies for managing cardiovascular diseases related to atherosclerosis and providing insights into the broader clinical applications of SGLT2 inhibitors.