Additionally, UA-induced activation of RAGE promotes the expression and extracellular release of high mobility group box 1 protein (HMGB1) by endothelial cells, lymphocytes, monocyte-derived macrophages, and vascular smooth muscle cells.87,283,284 The interaction between HMGB1 and RAGE amplifies the inflammatory cascade, contributing to cell apoptosis and endothelial dysfunction, resulted to CVD or CKD.277,285 This dysregulation of the HMGB1-RAGE pathway further diminishes NO availability, exacerbating inflammation. The gene discussed is HMGB1; the disease is endothelial dysfunction.