title: The anti-inflammatory effects of exercise training promote atherosclerotic plaque stabilization in apolipoprotein E knockout mice with diabetic atherosclerosis.
abstract: 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 x10(3)μm(2)) compared to the control (325.485 ± 72.302 x10(3)μm(2)) and sedentary (340.188 ± 159.108 x 10(3)μm(2)) 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.
authors.affiliation: Biomedical Research Foundation, Academy of Athens, Athens, Greece. nikoskad@yahoo.com
authors.forename: N P E
authors.initials: NP
authors.lastname: Kadoglou
authors.forename: P
authors.initials: P
authors.lastname: Moustardas
authors.forename: A
authors.initials: A
authors.lastname: Kapelouzou
authors.forename: M
authors.initials: M
authors.lastname: Katsimpoulas
authors.forename: A
authors.initials: A
authors.lastname: Giagini
authors.forename: E
authors.initials: E
authors.lastname: Dede
authors.forename: N
authors.initials: N
authors.lastname: Kostomitsopoulos
authors.forename: P E
authors.initials: PE
authors.lastname: Karayannacos
authors.forename: A
authors.initials: A
authors.lastname: Kostakis
authors.forename: C D
authors.initials: CD
authors.lastname: Liapis
mesh_terms: D000818:Animals; D001057:Apolipoproteins E; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000628:therapy; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000628:therapy; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D051379:Mice; D018345:Mice, Knockout; D010805:Physical Conditioning, Animal; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*
chemical_list: D001057:Apolipoproteins E; D004041:Dietary Fats; D015850:Interleukin-6; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases
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