Abstract: Objectives Endothelial dysfunction is the main cause of cardiovascular disease (CVD) in peritoneal dialysis (PD) patients. This study mimicked the high glucose condition of dialysate, and observed the role of adipocytes on the expression of ICAM-1 in endothelial cells, aiming to explore the mechanism of endothelial dysfunction. Methods 3T3-L1 cells were differentiated into mature adipocytes. Endothelial cells (ECs) were divided into six groups according to the medium used: blank control group (ECs cultured in DMEM), high glucose group (ECs treated with 139 mmol/L glucose), high mannitol group (ECs treated with 139 mmol/L mannitol), control-adipocyte group (ECs treated with the supernatant of adipocytes in DMEM), glucose-adipocyte group (ECs treated with the supernatant of adipocytes in higher glucose concentration), and mannitol-adipocyte group (ECs treated with the supernatant of adipocytes in higher mannitol concentration). Proliferation of ECs in 24h was measured by cell counting kit-8 (CCK-8) assay. Expression of tumor necrosis factor-α (TNF-α) by adipocytes was measured by enzyme-linked immunosorbent assay (ELISA). ICAM-1 level with or without the addition of SB203580 (a blocker of p38 mitogen-activated protein kinase, MAPK) in ECs was detected by western blot. Results More than 90% of the 3T3-L1 cells differentiated into adipocytes. The proliferation of ECs was promoted by the treatment of ECs with high glucose, high mannitol, super-natant of adipocytes in high glucose or high mannitol (high glucose group/control group, 1.600 ± 0.104 vs. 1.000±0.000, t=9.954, P=0.010; high mannitol group/control group, 1.240±0.100 vs. 1.000±0.000, t=4.157, P= 0.014; glucose- adipocyte group/control- adipocyte group, 1.563 ± 0.181 vs. 1.213 ± 0.097, t=2.945, P=0.042; mannitol- adipocyte group/control- adipocyte group, 1.520±1.473 vs. 1.213±0.097, t=3.010, P=0.040). High glucose significantly promoted the production of TNF- α in adipocytes (2515.313 ± 277.434 vs. 788.683 ± 167.267, t=9.232, P=0.001). The supernatant of high glucose treated adipocytes significantly promoted the expression of ICAM-1 in endothelial cells (1.533±0.058 vs. 1.133±0.153, t=4.243, P=0.013), and this promotion was partially inhibited by the p38 MAPK blocker SB203580 (0.850±0.111 vs. 1.124±0.108, t=- 3.053, P= 0.038). Conclusion Adipocytes exposed to high glucose promoted the expression of ICAM-1 in endothelial cells through TNF-α - p38 MAPK signal pathway. This process may relate to endothelial dysfunction and cardiovascular events in PD patients.

Key words: peritoneal dialysis, adipocytes, endothelial dysfunction, ICAM-1, cardiovasucular disease