Idebenone protects against oxidized low density lipoprotein induced mitochondrial dysfunction in vascular endothelial cells via GSK3β/β-catenin signalling pathways.
The early stages of the atherosclerotic process are initiated by accumulation of oxidized low-density lipoprotein (oxLDL) and damage to the structure or function of the endothelium. Antioxidant supplementation may be a plausible strategy to prevent atherosclerotic disease by quenching excessive reactive oxidative species. In the present study, we demonstrated that idebenone at suitable concentrations significantly prevented oxLDL-induced endothelial dysfunction. The underlying mechanisms of idebenone included inhibition of oxidative damage, suppression of the down-regulation of Bcl-2 and up-regulation of Bax and cleaved caspase-3 in human umbilical vein endothelial cells (HUVECs) exposed to oxLDL. Moreover, idebenone pretreatment inhibited oxLDL-mediated HUVECs damage by attenuating lipid peroxidation and promoting SOD activity. Finally, pro-incubation with idebenone inhibited mitochondrial dysfunction induced by oxLDL through the mitochondrial-dependent apoptotic pathway and GSK3β/β-catenin signalling pathways. In summary, idebenone is a promising agent in the treatment or prevention of atherosclerosis via inhibiting oxidative stress and improving mitochondrial function.
Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China; Key Laboratory for Experimental Teratology of the Ministry of Education, Brain Science Research Institute, Shandong University, Jinan, Shandong 250012, China.
Pengfei
P
Lin
Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China; Department of Neurology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, China.
Junling
J
Liu
Department of Neurology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, China.
Ming
M
Ren
Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
Kunqian
K
Ji
Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
Ling
L
Li
Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
Bin
B
Zhang
Key Laboratory of Experimental Teratology, Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China.
Yaoqin
Y
Gong
Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China; Key Laboratory for Experimental Teratology of the Ministry of Education, Brain Science Research Institute, Shandong University, Jinan, Shandong 250012, China. Electronic address: chuanzhuyan@163.com.
Chuanzhu
C
Yan
D000975:Antioxidants; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008077:Lipoproteins, LDL / Q000008:administration & dosage*; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051176:beta Catenin / Q000378:metabolism*
D000975:Antioxidants; C495270:CTNNB1 protein, human; D008077:Lipoproteins, LDL; D051176:beta Catenin; C099252:oxidized low density lipoprotein; D014451:Ubiquinone; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C036619:idebenone
Apoptosis; GSK3β/β-catenin signallingpathways; Idebenone; Mitochondria; oxLDL