Apolipoprotein A-I attenuates peritoneal fibrosis associated with peritoneal dialysis by inhibiting oxidative stress and inflammation
Jing Lü, Jie Gao, Jing Sun, Haiping Wang, Huijuan Sun, Qian Huang, Yao Zhang, Shuo Zhong
Abstract
Apolipoprotein A-I (apoA-I), 90% of which is present in high-density lipoprotein (HDL), is the main constituent of HDL, has anti-inflammatory and anti-oxidant properties, and has received extensive attention in anti-atherosclerosis. Yet little is known about apoA-I ’s role in peritoneal dialysis. In this study, by analyzing PD patients ( n = 81), we found that decreased apoA/HDL-C ratio is significantly associated with rapid decline in peritoneal function. Further studies were performed in animal experiments to determine the ascendancy of apolipoprotein A-I mimetic peptide (D-4F) on peritoneum, we found that D-4F administration reduced peritoneal fibrosis and peritoneal endothelial mesenchymal transformation (EMT) induced by high glucose peritoneal dialysate, such as N-cadherin, Fibronectin, Vimentin, and α-smooth muscle actin (α-SMA) expression decreased. In mechanism, D-4F can significantly inhibit Smad2/3 phosphorylation, which is the major pathway leading to fibrosis. Furthermore, D-4F treatment inhibited NADPH oxidase and thiobarbituric acid reactive substances (TBARS) expression, increased the activity of certain enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Finally, treatment with D-4F inhibits the expression of interleukins-6(IL-6), Interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α). Taken together, based on the above research evidence, apoA-I and its peptide mimic may regulate the oxidative stress, TGF- β1/Smads signaling pathway and inflammatory response to reduce peritoneal fibrosis due to peritoneal dialysis.