TY - JOUR
T1 - Probucol Protects Endothelial Progenitor Cells Against Oxidized Low-Density Lipoprotein via Suppression of Reactive Oxygen Species Formation in Vivo
AU - Zhang, Qingbin
AU - Chen, Liming
AU - Si, Zhihua
AU - Bu, Haoran
AU - Narasimhulu, Chandrakala A.
AU - Song, Xueling
AU - Cui, Ming Yu
AU - Liu, Hang
AU - Lu, Tiewei
AU - He, Guanglong
AU - Parthasarathy, Sampath
AU - Cui, Lianqun
AU - Liu, Zhenguo
AU - Cui, Yuqi
N1 - Funding Information:
This work was supported by a U.S. NIH grants to ZL (NIH R 爃猀 HL 爃笃瘃砃眃爀 and RO 猀
Funding Information:
Acknowledgment: This work was supported by a U.S. NIH grants to ZL (NIH R01 HL094650 and RO1 HL124122) and Shandong Provincial Science and Technology Development Grants to LC (2010GSF10272 and 2008GG3002018).
Publisher Copyright:
© 2016 The Author(s) Published by S. Karger AG, Basel.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
KW - Endothelial progenitor cells
KW - Oxidized low-density lipoprotein
KW - Probucol
KW - Reactive oxygen species
UR - https://www.scopus.com/pages/publications/84976286515
U2 - 10.1159/000445608
DO - 10.1159/000445608
M3 - Article
C2 - 27322674
AN - SCOPUS:84976286515
SN - 1015-8987
VL - 39
SP - 89
EP - 101
JO - Cellular Physiology and Biochemistry
JF - Cellular Physiology and Biochemistry
IS - 1
ER -