serval:BIB_E6947BD847EE
Voluntary Exercise Stabilizes Established Angiotensin II-Dependent Atherosclerosis in Mice through Systemic Anti-Inflammatory Effects.
10.1371/journal.pone.0143536
000365862600080
26600018
Pellegrin
M.
author
Aubert
J.F.
author
Bouzourène
K.
author
Amstutz
C.
author
Mazzolai
L.
author
article
2015
Plos One
1932-6203
1932-6203
journal
10
11
e0143536
We have previously demonstrated that exercise training prevents the development of Angiotensin (Ang) II-induced atherosclerosis and vulnerable plaques in Apolipoprotein E-deficient (ApoE-/-) mice. In this report, we investigated whether exercise attenuates progression and promotes stability in pre-established vulnerable lesions. To this end, ApoE-/- mice with already established Ang II-mediated advanced and vulnerable lesions (2-kidney, 1-clip [2K1C] renovascular hypertension model), were subjected to sedentary (SED) or voluntary wheel running training (EXE) regimens for 4 weeks. Mean blood pressure and plasma renin activity did not significantly differ between the two groups, while total plasma cholesterol significantly decreased in 2K1C EXE mice. Aortic plaque size was significantly reduced by 63% in 2K1C EXE compared to SED mice. Plaque stability score was significantly higher in 2K1C EXE mice than in SED ones. Aortic ICAM-1 mRNA expression was significantly down-regulated following EXE. Moreover, EXE significantly down-regulated splenic pro-inflammatory cytokines IL-18, and IL-1β mRNA expression while increasing that of anti-inflammatory cytokine IL-4. Reduction in plasma IL-18 levels was also observed in response to EXE. There was no significant difference in aortic and splenic Th1/Th2 and M1/M2 polarization markers mRNA expression between the two groups. Our results indicate that voluntary EXE is effective in slowing progression and promoting stabilization of pre-existing Ang II-dependent vulnerable lesions by ameliorating systemic inflammatory state. Our findings support a therapeutic role for voluntary EXE in patients with established atherosclerosis.
Angiotensin II/metabolism
Angiotensin II/pharmacology
Animals
Anti-Inflammatory Agents/pharmacology
Apolipoproteins E/deficiency
Atherosclerosis/genetics
Atherosclerosis/metabolism
Biomarkers
CD4-Positive T-Lymphocytes/immunology
CD4-Positive T-Lymphocytes/metabolism
Cytokines/blood
Cytokines/metabolism
Disease Models, Animal
Inflammation Mediators/blood
Inflammation Mediators/metabolism
Macrophages/immunology
Macrophages/metabolism
Mice
Mice, Knockout
Phenotype
Physical Conditioning, Animal
Plaque, Atherosclerotic/metabolism
eng
60_published
true
peer-reviewed
Publication types: Journal Article Publication Status: epublish
University of Lausanne
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