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

  • N.P.E. Kadoglou | Biomedical Research Foundation, Academy of Athens, Greece.
  • P. Moustardas
  • A. Kapelouzou
  • M. Katsimpoulas
  • A. Giagini
  • E. Dede
  • N. Kostomitsopoulos
  • P.E. Karayannacos
  • A. Kostakis
  • C.D. Liapis


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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Author Biography

N.P.E. Kadoglou, Biomedical Research Foundation, Academy of Athens
Center of Experimental Surgery
Original Papers
Supporting Agencies
Co-funded by the Operational Program "Competitiveness and Entrepreneurship" and Regional Operational Programmes of the National Strategic Reference Framework (NSRF) 2007-2013.
diabetes, atherosclerosis, exercise, matrix metalloproteinases, plaque stability
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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.