Effect of tocopherol on atherosclerosis, vascular function and inflammation in Apolipoprotein E knockout mice with subtotal nephrectomy

Shing, Cecilia, Fassett, Robert, Peake, Jonathan, & Coombes, Jeff S. (2014) Effect of tocopherol on atherosclerosis, vascular function and inflammation in Apolipoprotein E knockout mice with subtotal nephrectomy. Cardiovascular Therapeutics, 32(6), pp. 270-275.

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Background/Aims: Inflammation and endothelial dysfunction contribute to cardiovascular disease, prevalent in chronic kidney disease (CKD). Antioxidant supplements such as tocopherols may reduce inflammation and atherosclerosis. This study aimed to investigate the effect of tocopherol supplementation on vascular function, aortic plaque formation, and inflammation in apolipoprotein E−/− mice with 5/6 nephrectomy as a model of combined cardiovascular and kidney disease.

Methods: Nephrectomized mice were assigned to a normal chow diet group (normal chow), a group receiving 1000 mg/kg diet of α-tocopherol supplementation or a group receiving 1000 mg/kg diet mixed-tocopherol (60% γ-tocopherol).

Results: Following 12 weeks, in vitro aortic endothelial-independent relaxation was enhanced with both α-tocopherol and mixed-tocopherol (P < 0.05), while mixed-tocopherol enhanced aortic contraction at noradrenaline concentrations of 3 × 10−7 M to 3 × 10−5 M (P < 0.05), when compared to normal chow. Supplementation with α- and mixed-tocopherol reduced systemic concentrations of IL-6 (P < 0.001 and P < 0.001, respectively) and IL-10 (P < 0.05 and P < 0.001, respectively), while α-tocopherol also reduced MCP-1 (P < 0.05) and tumor necrosis factor (TNF)-α (P < 0.05). Aortic sinus plaque area was significantly reduced with α-tocopherol supplementation when compared to normal chow (P < 0.01).

Conclusion: Tocopherol supplementation favorably influenced vascular function and cytokine profile, while it was also effective in reducing atherosclerosis in the apolipoprotein E−/− mouse with CKD.

Impact and interest:

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ID Code: 79498
Item Type: Journal Article
Refereed: Yes
Keywords: Cardiovascular disease; Chronic kidney disease; Cytokines; Plaque; Tocopherol
DOI: 10.1111/1755-5922.12096
ISSN: 1755-5922
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > NUTRITION AND DIETETICS (111100) > Nutritional Physiology (111103)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2014 John Wiley & Sons Ltd
Copyright Statement: This is the accepted version of the following article: Shing, C. M., Fassett, R. G., Peake, J. M. and Coombes, J. S. (2014), Effect of Tocopherol on Atherosclerosis, Vascular Function, and Inflammation in Apolipoprotein E Knockout Mice with Subtotal Nephrectomy. Cardiovascular Therapeutics, 32: 270–275. doi: 10.1111/1755-5922.12096, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/1755-5922.12096/full
Deposited On: 16 Dec 2014 00:46
Last Modified: 04 Jan 2016 16:28

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