Dysfunction of endothelial progenitor cells in hyperlipidemic rats involves the increase of NADPH oxidase derived reactive oxygen species production.
NADPH oxidase (NOX) is a major source of reactive oxygen species (ROS) in the body and it plays a key role in mediation of oxidative injury in the cardiovascular system. The purposes of this study are to evaluate the status of NOX in endothelial progenitor cells (EPCs) of hyperlipidemic rats and to determine whether NOX-derived ROS promotes the dysfunction of EPCs. The rats were fed on a high-fat diet for 8 weeks to establish a hyperlipidemic rat model, which showed the increased plasma lipids and the impaired functions of circulating EPCs (including the reduced abilities in migration and adhesion) accompanied by an increase in NOX activity and ROS production. Next, EPCs were isolated from normal rats and they were treated with oxidized low-density lipoprotein (ox-LDL) (100 μg/mL) for 24 h to induce a dysfunctional model in vitro. In agreement with our findings in vivo, ox-LDL treatment increased the dysfunctions of EPCs concomitant with an increase in NOX activity and ROS production; these phenomena were reversed by the NOX inhibitor. Based on these observations, we conclude that NOX-derived ROS involved in the dysfunctions of circulating EPCs in hyperlipidemic rats and inhibition of NOX might provide a novel strategy to improve EPC functions in hyperlipidemia.
a Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Ting-Bo
TB
Li
a Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Jie-Jie
JJ
Zhang
a Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Bin
B
Liu
b Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha 410013, China.
Xiu-Ju
XJ
Luo
c Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
Qi-Lin
QL
Ma
a Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.|d Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Jun
J
Peng
D000818:Animals; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006949:Hyperlipidemias / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
D004791:Enzyme Inhibitors; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D019255:NADPH Oxidases
NADPH oxidase; NADPH oxydase; cellules endothéliales progénitrices; dérivés réactifs de l’oxygène; endothelial progenitor cells; hyperlipidemia; hyperlipidémie; lipoprotéines de basse densité oxydées; oxidized low-density lipoprotein; reactive oxygen species