Long-term exercise stabilizes atherosclerotic plaque in ApoE knockout mice.
OBJECTIVE
Exercise is known to reduce cardiovascular mortality. However, the precise mechanisms are still unknown. Because atherosclerotic plaque destabilization and rupture leads to dramatic cardiovascular events, stabilization of plaque might be regarded as an important goal of an exercise preventive therapy. The present study examined the plaque-stabilizing effect of long-term exercise in experimental atherosclerosis using apolipoprotein E-deficient mice (ApoE(-/-)).


METHODS
ApoE(-/-) mice were subjected to 6 months of swimming exercise. A group of sedentary animals were used as controls. Morphometry and characteristics of atherosclerotic plaque stability were assessed in aortic sinus by immunohistochemistry. Aortic levels of total protein kinase Akt (protein kinase B), phosphorylated Akt at Ser(473) (p-Akt), total endothelial nitric oxide synthase (eNOS), and phosphorylated eNOS at Ser(1177) (p-eNOS) were assessed by Western blotting.


RESULTS
Exercised mice developed a more stable plaque phenotype as shown by decreased macrophage and increased smooth muscle cell content. Protein expressions of Akt, p-Akt, eNOS, and p-eNOS were not modulated by exercise.


CONCLUSIONS
Long-term exercise promotes plaque stability in ApoE(-/-) mice. The Akt-mediated eNOS phosphorylation pathway seems not to be the primary molecular mechanism.
Pellegrin
Maxime
M
EA-4267/2SBP, University of Franche-Comté, Besançon, France. Maxime.Pellegrin@chuv.ch
Miguet-Alfonsi
Carole
C
Bouzourene
Karima
K
Aubert
Jean-François
JF
Deckert
Valérie
V
Berthelot
Alain
A
Mazzolai
Lucia
L
Laurant
Pascal
P
D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology*; D050197:Atherosclerosis / Q000503:physiopathology / Q000517:prevention & control*; D015153:Blotting, Western; D007120:Immunochemistry; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D011897:Random Allocation; D057185:Sedentary Behavior; D013550:Swimming / Q000502:physiology*
D001057:Apolipoproteins E; D008055:Lipids