Probucol Protects Endothelial Progenitor Cells Against Oxidized Low-Density Lipoprotein via Suppression of Reactive Oxygen Species Formation In Vivo

Abstract

Background/Aims: Oxidized low-density lipoprotein (ox-LDL) is a major component of hyperlipidemia and contributes to atherosclerosis. Endothelial progenitor cells (EPCs) play an important role in preventing atherosclerosis and notably decreased in hyperlipidemia. Ox-LDL and ox-LDL-related reactive oxygen species (ROS) have deleterious effects on EPCs. Probucol as an antioxidant and anti-inflammatory drug reduces ROS production. The present study was to determine if probucol could protect EPCs from ox-LDL in vivo and to investigate the potential mechanisms. Methods: ox-LDL was injected into male C57BL/6 mice for 3 days with or without probucol treatment with PBS as control. Bone marrow (BM) fluid, serum, circulating mononuclear cells (MNCs) and EPCs were collected for analysis. Results: the increased extracellular ROS in BM, serum and blood intracellular ROS production in the mice with ox-LDL treatment in association with a significant reduction of circulating MNCs and EPCs were restored with Probucol treatment. A significant increase in the serum ox-LDL and C-reactive protein and decrease in superoxide dismutase and circulating MNCs and EPCs were observed in hyperlipidemic patients that were effectively reversed with probucol treatment. Conclusion: these data suggested that probucol could protect EPCs from ox-LDL through inhibition of ROS production in vivo.

PTPRO Promotes Oxidized Low-Density Lipoprotein Induced Oxidative Stress and Cell Apoptosis through Toll-Like Receptor 4/Nuclear Factor κB Pathway

“…These suggested that PTPRO played vital roles in the formation of macrophage-derived foam cells. Generally, in ox-LDL induced AS, increased cell apoptosis and oxidative stress of macrophages was the main mechanism [29], so we detected that whether PTPRO functionally affected the cell apoptosis and oxidative stress of macrophages. As the results showed that over-expression of PTPRO resulted in improved cell apoptosis and oxidative stress and depletion of PTPRO reversed these effects.…”

Oxidized low‐density lipoprotein stimulates epithelial sodium channels in endothelial cells of mouse thoracic aorta

“…This feedback implies that enhanced ENaC activity reduces NO production in endothelial cells and that, conversely, a reduction in NO will relieve its inhibitory effects on ENaC activity. ox ‐LDL is a product of chronic oxidative stress; it is also a potent inducer of oxidative stress, as ox‐LDL injections have been shown to increase both bone marrow and blood ROS levels in mice (Zhang et al , ). Importantly, incubation of cultured human aortic endothelial cells with ox‐LDL enhances ROS via the phosphorylation of p66Shc, an important mediator of oxidative stress (Shi et al , ).…”

Probucol Reduces Testicular Torsion/Detorsion‐Induced Ischemia/Reperfusion Injury in Rats

“…Probucol is a clinically used lipid-lowering drug with potent antioxidant and anti-inflammatory properties [ 7 ]. Early studies have demonstrated that probucol can attenuate ischemia-reperfusion injury in the kidney, heart, and brain [ 8 – 10 ].…”