VASCULAR ENDOTHELIAL DYSFUNCTION IMPROVEMENTS IN PATIENTS WITH UREMIA USING PENTOXIFYLLINE-SUPPRESSING NLRP3 EXPRESSIONS AND HMGB1 RELEASE.

This study aimed to investigate the protective effect of pentoxifylline (PTX) on vascular endothelial dysfunction in uremia. The human aortic endothelial cells (HAECs) required for the experiments were all obtained from the National Collection of Authenticated Cell Cultures (Salisbury, UK). The permeability of HAECs was assessed. Each group had six samples. Compared with the healthy volunteer group, HAEC proliferation in the 20% uremia group was significantly inhibited after 72 h ( P < 0.001), co-localization of nucleotide-binding domain, leucine-rich repeat-containing receptor family pyrin domain-containing 3 (NLRP3) and apoptosis-associated speck-like (ASC) protein induced by uremic serum was enhanced ( P < 0.01) and high mobility group box 1 (HMGB1) release was increased (0.594 ± 0.057, P = 0.03). The co-immunoprecipitation of NLRP3, ASC, and HMGB1 induced by uremic toxin was also enhanced ( P < 0.01), and PTX inhibited this phenomenon. The expression of NLRP3 (0.810 ± 0.032, P = 0.02) and caspase-1 (0.580 ± 0.041, P = 0.03) was increased, whereas the expression of ZO-1 (0.255 ± 0.038, P = 0.03) and VE-cadherin (0.0546 ± 0.053, P = 0.02) was decreased in the uremia group; compared with the healthy volunteer group, treated with PTX (NLRP3, 0.298 ± 0.042, P = 0.03; caspase-1, 0.310 ± 0.021, P = 0.03; ZO-1, 0.412 ± 0.028, P = 0.02; VE-cadherin, 0.150 ± 0.034, P = 0.02) and MCC950 (NLRP3, 0.432 ± 0.022, P = 0.03; caspase-1, 0.067 ± 0.031, P > 0.05; ZO-1, 0.457 ± 0.026, P = 0.03; VE-cadherin, 0.286 ± 0.017, P = 0.03) these lessened this trend. Pentoxifylline promoted the HAEC permeability mediated by uremic toxins (1.507 ± 0.012, P = 0.02). In conclusion, PTX enhances the release of HMGB1, which is dependent on NLRP3 activation, and consequently exerts positive effects on interconnecting proteins, ultimately leading to an improvement in vascular permeability.