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


CONCLUSIONS
these data suggested that probucol could protect EPCs from ox-LDL through inhibition of ROS production in vivo.
Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China.
Qingbin
Q
Zhang
Liming
L
Chen
Zhihua
Z
Si
Haoran
H
Bu
Chandrakala A
CA
Narasimhulu
Xueling
X
Song
Ming-Yu
MY
Cui
Hang
H
Liu
Tiewei
T
Lu
Guanglong
G
He
Sampath
S
Parthasarathy
Lianqun
L
Cui
Zhenguo
Z
Liu
Yuqi
Y
Cui
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011341:Probucol / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000097:blood / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein; D013482:Superoxide Dismutase; D011341:Probucol