Inhibitory effects of fenofibrate on apoptosis and cell proliferation in human endothelial cells in high glucose

Fenofibrate has beneficial effects on the progression and clinical emergence of atherosclerosis in normoglycemic and in diabetic patients. Given the involvement of endothelium in these processes, we speculated that fenofibrate may influence endothelial cell apoptosis and proliferation, regulators of endothelium integrity. Fenofibrate effects on apoptosis and proliferation were studied in human umbilical vein endothelial cells under normal (5.5 mmol/l, NG) and high (22 mmol/l, HG) glucose with or without fenofibrate (50 micromol/l). Apoptosis was evaluated by annexin V, by poly(ADP-ribose) polymerase protein cleavage, and cyclooxygenase-2 (COX-2), Bax/Bcl-2, and p53 protein levels; proliferation was assessed by determining cell cycle phase distribution and the amounts of the cell cycle regulators E2F1, cyclin D1, E1, and A and the levels of the hyper-phosphorylated form of the retinoblastoma protein (ppRb). HG resulted in increased (p