The anti-inflammatory effects of exercise training promote atherosclerotic plaque stabilization in apolipoprotein E knockout mice with diabetic atherosclerosis

Submitted: 4 March 2012
Accepted: 27 July 2012
Published: 25 March 2013
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Physical exercise is the cornerstone of cardiovascular disease treatment. The present study investigated whether exercise training affects atherosclerotic plaque composition through the modification of inflammatory-related pathways in apolipoprotein E knockout (apoE-/-) mice with diabetic atherosclerosis. Forty-five male apoE-/- mice were randomized into three equivalent (n=15) groups: control (CO), sedentary (SED), and exercise (EX). Diabetes was induced by streptozotocin administration. High-fat diet was administered to all groups for 12 weeks. Afterwards, CO mice were euthanatized, while the sedentary and exercise groups continued high-fat diet for 6 additional weeks. Exercising mice followed an exercise program on motorized-treadmill (5 times/week, 60 min/session). Then, blood samples and atherosclerotic plaques in the aortic root were examined. A considerable (P<0.001) regression of the atherosclerotic lesions was observed in the exercise group (180.339±75.613 x103μm2) compared to the control (325.485±72.302 x103μm2) and sedentary (340.188±159.108 x103μm2) groups. We found decreased macrophages, matrix metalloproteinase-2 (MMP-2), MMP-3, MMP-8 and interleukin-6 (IL-6) concentrations (P<0.05) in the atherosclerotic plaques of the exercise group. Compared to both control and sedentary groups, exercise training significantly increased collagen (P<0.05), elastin (P<0.001), and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) (P<0.001) content in the atherosclerotic plaques. Those effects paralleled with increased fibrous cap thickness and less internal elastic lamina ruptures after exercise training (P<0.05), while body-weight and lipid parameters did not significantly change. Plasma MMP-2 and MMP-3 concentrations in atherosclerotic tissues followed a similar trend. From our study we can conclude that exercise training reduces and stabilizes atherosclerotic lesions in apoE-/- mice with diabetic atherosclerosis. A favorable modification of the inflammatory regulators seems to explain those beneficial effects.

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Supporting Agencies

Co-funded by the Operational Program "Competitiveness and Entrepreneurship" and Regional Operational Programmes of the National Strategic Reference Framework (NSRF) 2007-2013.
N.P.E. Kadoglou, Biomedical Research Foundation, Academy of Athens
Center of Experimental Surgery

How to Cite

Kadoglou, N., Moustardas, P., Kapelouzou, A., Katsimpoulas, M., Giagini, A., Dede, E., Kostomitsopoulos, N., Karayannacos, P., Kostakis, A., & Liapis, C. (2013). The anti-inflammatory effects of exercise training promote atherosclerotic plaque stabilization in apolipoprotein E knockout mice with diabetic atherosclerosis. European Journal of Histochemistry, 57(1), e3. https://doi.org/10.4081/ejh.2013.e3