期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 52, 期 5, 页码 841-849出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2011.11.026
关键词
Metabolic syndrome; MitoQ; Atherosclerosis; Mitochondria
资金
- British Heart Foundation (BHF) [RG08/009/25841, PG/05/08]
- Diabetes and Wellness Foundation
- BBSRC
- Wellcome Trust [072829/Z/03/Z]
- MRC
- Hepadip grant
- Cambridge NIHR Biomedical Research Centre
- MRC [G0802051, G0800784, MC_U105663142, MC_UP_A090_1006, G1000847] Funding Source: UKRI
- British Heart Foundation [RG/08/009/25841] Funding Source: researchfish
- Medical Research Council [G0800784, MC_UP_A090_1006, MC_U105663142, G0802051, G0600717B, G1000847] Funding Source: researchfish
A number of recent studies suggest that mitochondrial oxidative damage may be associated with atherosclerosis and the metabolic syndrome. However, much of the evidence linking mitochondrial oxidative damage and excess reactive oxygen species (ROS) with these pathologies is circumstantial. Consequently the importance of mitochondria! ROS in the etiology of these disorders is unclear. Furthermore, the potential of decreasing mitochondrial ROS as a therapy for these indications is not known. We assessed the impact of decreasing mitochondrial oxidative damage and ROS with the mitochondria-targeted antioxidant MitoQ in models of atherosclerosis and the metabolic syndrome (fat-fed ApoE(-/-) mice and ATM(+/-)/ApoE(-/-) mice, which are also haploinsufficient for the protein kinase, ataxia telangiectasia mutated (ATM). MitoQ administered orally for 14 weeks prevented the increased adiposity, hypercholesterolemia, and hypertriglyceridemia associated with the metabolic syndrome. MitoQ also corrected hyperglycemia and hepatic steatosis, induced changes in multiple metabolically relevant lipid species, and decreased DNA oxidative damage (8-oxo-G) in multiple organs. Although MitoQ did not affect overall atherosclerotic plaque area in fat-fed ATM(+/+)/ApoE(-/-) and ATM(+/-)/ApoE(-/-) mice, MitoQ reduced the macrophage content and cell proliferation within plaques and 8-oxo-G. MitoQ also significantly reduced mtDNA oxidative damage in the liver. Our data suggest that MitoQ inhibits the development of multiple features of the metabolic syndrome in these mice by affecting redox signaling pathways that depend on mitochondria! ROS such as hydrogen peroxide. These findings strengthen the growing view that elevated mitochondrial ROS contributes to the etiology of the metabolic syndrome and suggest a potential therapeutic role for mitochondria-targeted antioxidants. (C) 2011 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据