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Effects of exercise training and RhoA/ROCK inhibition on plaque in ApoE(-/-) mice.
MedLine Citation:
PMID:  22525349     Owner:  NLM     Status:  Publisher    
BACKGROUND: The molecular mechanisms of exercise-induced cardioprotection are poorly understood. We recently reported that exercise training down-regulated gene expression of the Ras homolog gene family member A (RhoA). RhoA and its first effectors, the Rho-kinases (ROCK), have already been implicated in the pathogenesis of cardiovascular disease. The aim of this study was to compare the effects of a RhoA/ROCK inhibitor (fasudil) and exercise in the Apolipoprotein E knockout (ApoE(-/-)) mouse model of atherosclerosis. METHODS: Four groups of 14week old ApoE(-/-) mice were randomised as follows (n=12/group): i) sedentary controls (Cont); ii) fasudil (Fas) treatment (100mg/kg bodyweight/day) for 8weeks; iii) exercise intervention (Ex:free access to running wheel for 8weeks) and iv) exercise intervention and fasudil treatment (ExFas) for 8weeks. RESULTS: Phosphorylation of myosin light chain was significantly reduced in the brachiocephalic artery of all treatment groups compared with sedentary controls, implying an inhibitory effect of exercise and fasudil on the RhoA/ROCK pathway. Furthermore, atherosclerotic lesions were significantly smaller in all treatment and intervention groups compared with the control group (Fas: 34.7%, Ex: 48.3%, ExFas: 40.9% less than Control). The intima:media ratio was reduced by both exercise intervention and fasudil treatment alone or in combination (Fas: 23.6%, Ex: 35.5%, ExFas: 43.9% less than Control). Exercise alone and fasudil treatment alone also showed similar effects on plaque composition, increasing both smooth muscle cell and macrophage density. CONCLUSION: These results suggest that the protective effects of exercise on atherogenesis are similar to the inhibitory effects on the RhoA/ROCK signalling pathway.
Aya Matsumoto; Helga D Manthey; Susan A Marsh; Robert G Fassett; Judy B de Haan; Barbara E Rolfe; Jeff S Coombes
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-21
Journal Detail:
Title:  International journal of cardiology     Volume:  -     ISSN:  1874-1754     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
School of Human Movement Studies, The University of Queensland, Brisbane, Queensland, Australia.
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