title: Swimming reduces the severity of atherosclerosis in apolipoprotein E deficient mice by antioxidant effects.
abstract: OBJECTIVE
  It was shown that aerobic exercise training may protect against the development of atherosclerosis. However, the precise mechanisms are still unknown. We assessed the hypothesis that exercise training reduced the severity of experimental atherosclerosis in apolipoprotein (apo) E-deficient mice by antioxidant effects.
  
  
  METHODS
  Exercise training (45 min swimming, 3 times/week) was conducted on apo E-deficient mice fed a high fat diet. Over 8 and 16 weeks on alternate days, mice were treated with and without exercise, and additional exercise-treated mice were orally given 25 mg/kg/day of NG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase (NOS). In addition, the effect of L-arginine against L-NAME was also tested.
  
  
  RESULTS
  Fatty streak formation at 8 weeks and fibrofatty plaques at 16 weeks developed in apo E-deficient mice fed a high fat diet, and were suppressed in mice treated with swimming for 8 and 16 weeks. In contrast, atherosclerotic lesions were not ameliorated in mice treated with exercise training associated with oral L-NAME. However, in mice treated with swimming associated with L-NAME and L-arginine, the atherosclerotic lesions were reduced. Immunohistochemical analysis revealed that macrophage and CD4+ cell accumulation in the fatty streak lesions was suppressed in mice treated with exercise, but not in those treated with exercise associated with L-NAME administration. The severity of atherosclerotic lesions was inversely correlated with the endothelial NOS expression and the expression of an endogenous antioxidant protein, thioredoxin. Namely, the expression of thioredoxin in mice treated with exercise was suppressed compared with mice without exercise. Plasma thiobarbituric acid-reactive substance levels were significantly lower in groups with exercise than in those without exercise or with exercise associated with L-NAME administration, suggesting exercise-induced less lipid peroxidation. Differences in lesion area did not correlate with any significant alterations in serum lipid levels. The exercise load used in the current study did not affect energy metabolism efficacies in the hearts.
  
  
  CONCLUSIONS
  Exercise training, in which the load did not affect energy metabolism efficacy of the heart, suppressed atherosclerosis by antioxidant effects via the vascular NO system.
authors: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan.
authors: Taka-aki
authors: TA
authors: Okabe
authors: Kana
authors: K
authors: Shimada
authors: Miki
authors: M
authors: Hattori
authors: Toshinori
authors: T
authors: Murayama
authors: Masayuki
authors: M
authors: Yokode
authors: Toru
authors: T
authors: Kita
authors: Chiharu
authors: C
authors: Kishimoto
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001011:Aorta / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D001120:Arginine / Q000494:pharmacology; D050197:Atherosclerosis / Q000378:metabolism / Q000517:prevention & control*; D004041:Dietary Fats / Q000008:administration & dosage; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010805:Physical Conditioning, Animal / Q000502:physiology*; D013550:Swimming / Q000502:physiology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D004041:Dietary Fats; D017392:Thiobarbituric Acid Reactive Substances; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester