期刊
ATHEROSCLEROSIS
卷 240, 期 1, 页码 234-241出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2015.03.012
关键词
TEMPOL; Nitroxide; Atherosclerosis; Cardiovascular disease; Lipid; Inflammatory cytokines; Adipokines
资金
- Australian Research Council (ARC Centres of Excellence and Discovery Programs) [CE0561607, DP0988311]
- Community Grant
- University Postgraduate Award from the University of Sydney
Objective: The nitroxide compound TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl radical) has been shown to prevent obesity-induced changes in adipokines in cell and animal systems. In this study we investigated whether supplementation with TEMPOL inhibits inflammation and atherosclerosis in apoE(-/-) mice fed a high fat diet (HFD). Methods: ApoE(-/-) mice were fed for 12 weeks on standard chow diet or a high-fat diet. Half the mice were supplemented with 10 mg/g TEMPOL in their food. Plasma samples were analysed for triglycerides, cholesterol, low-and high-density lipoprotein cholesterol, inflammatory cytokines and markers (inter-leukin- 6, IL-6; monocyte-chemotactic protein, MCP-1; myeloperoxidase, MPO; serum amyloid A, SAA; adiponectin; leptin). Plaques in the aortic sinus were analysed for area, and content of collagen, lipid, macrophages and smooth muscle cells. Results: High fat feeding resulted in marked increases in body mass and plasma lipid levels. Dietary TEMPOL decreased both parameters. In the high-fat-fed mice significant elevations in plasma lipid levels and the inflammatory markers IL-6, MCP-1, MPO, SAA were detected, along with an increase in leptin and a decrease in adiponectin. TEMPOL supplementation reversed these effects. When compared to HFD-fed mice, TEMPOL supplementation increased plaque collagen content, decreased lipid content and increased macrophage numbers. Conclusions: These data indicate that in a well-established model of obesity-associated hyperlipidaemia and atherosclerosis, TEMPOL had a significant impact on body mass, atherosclerosis, hyperlipidaemia and inflammation. TEMPOL may therefore be of value in suppressing obesity, metabolic disorders and increasing atherosclerotic plaque stability. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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