Uremic Serum Induces Inflammation in Cultured Human Endothelial Cells and Triggers Vascular Repair Mechanisms

Inflammation and cardiovascular disease (CVD) are common in end-stage renal disease (ESRD) patients whose vascular endothelium is in direct contact with the uremic toxins found in the blood. These toxins are believed to affect vascular injury and repair process, which is impaired in ESRD patients. The exact mechanisms behind these interactions are not clear. So, we wanted to investigate what happens at the molecular level of endothelial cells when exposed to uremic serum from ESRD patients with diabetes and/or hypertension and its effect on the expression of molecules associated with vascular injury and repair. Cultured human endothelial cells (ECV304) were incubated in the presence of normal or uremic sera from ESRD patients with diabetes and/or hypertension. The expressions of monocyte chemoattractant protein 1 (MCP-1), vascular endothelial growth factor (VEGF), and stromal cell–derived factor 1 (SDF-1) were investigated in endothelial cells (ECV304) by real-time PCR and ELISA. The expression of MCP-1, VEGF, and SDF-1 was elevated in endothelial cells upon exposure to uremic sera from ESRD patients with diabetes and/or hypertension when compared with cells treated with healthy serum. MCP-1 expression in endothelial cells treated with uremic serum from ESRD patients with hypertension only was significantly increased compared with its expression in other cohorts. Exposure of endothelial cells to uremic serum causes endothelial injury and inflammation characterized by an increase in MCP-1 expression. This injury activates the initiation of vascular repair process in these cells by increasing the expression of VEGF and SDF-1. These molecules can be important biomarkers of chronic kidney disease–associated CVD.