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Allopurinol Attenuates Oxidative Stress and Cardiac Fibrosis in Angiotensin II-Induced Cardiac Diastolic Dysfunction.
MedLine Citation:
PMID:  20973927     Owner:  NLM     Status:  In-Data-Review    
Aims: Oxidative stress and fibrosis is implicated in cardiac remodeling and failure. We tested whether allopurinol could decrease myocardial oxidative stress and attenuate cardiac fibrosis and left ventricular diastolic dysfunction in angiotensin II (AngII)-induced hypertensive mice. Methodology: We used 8-week-old male C57BL/6J mice, in which angiotensin II was subcutaneously infused for 4 weeks to mimic cardiac remodeling and fibrosis. They were treated with either normal saline or allopurinol in daily doses, which did not lower blood pressure. Results: Allopurinol improved diastolic dysfunction in angiotensin II-induced hypertensive mice, which was associated with the amelioration of cardiac fibrosis. However, allopurinol showed no effect on the increased systolic blood pressure by angiotensin II infusion. The ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) [GSH/GSSG] was decreased and malondialdehyde levels were increased in the hearts of AngII-treated mice. Allopurinol also inhibited both the decrease in the GSH/GSSG ratio and the increase in malondialdehyde levels in the heart. Infusion of AngII-induced upregulation of transfer growth factor (TGF)-β1, Smad3 expression and downregulation of Smad7 expression. Treatment with allopurinol reduced cardiac levels of TGF-β1, Smad3, and increased Smad7 expression. Conclusions: These results suggest that allopurinol prevents pathological remodeling of the heart in AngII-induced hypertensive mice. The antioxidative effect of allopurinol contributes to the regression of AngII-induced cardiac diastolic dysfunction. These effects of allopurinol to prevent cardiac fibrosis are mediated at least partly through modulation of the TGF-β1/Smad signaling pathway.
Nan Jia; Peixin Dong; Ying Ye; Cheng Qian; Qiuyan Dai
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Publication Detail:
Type:  Journal Article     Date:  2010-10-26
Journal Detail:
Title:  Cardiovascular therapeutics     Volume:  30     ISSN:  1755-5922     ISO Abbreviation:  Cardiovasc Ther     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101319630     Medline TA:  Cardiovasc Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  117-23     Citation Subset:  IM    
Copyright Information:
© 2010 Blackwell Publishing Ltd.
Ruijin Hospital, Shanghai Institute of Hypertension, Shanghai Jiao Tong University Medical School, Shanghai, PR China 200025 Department of Cardiology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, PR China 200080 Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, PR China 200011.
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