Document Detail


Inhibition of NADPH oxidase reduces myocardial oxidative stress and apoptosis and improves cardiac function in heart failure after myocardial infarction.
MedLine Citation:
PMID:  17603936     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Increases in NADPH oxidase activity, oxidative stress, and myocyte apoptosis coexist in failing hearts. In cardiac myocytes in vitro inhibition of NADPH oxidase reduces apoptosis. In this study, we tested the hypothesis that NADPH oxidase inhibition reduces myocyte apoptosis and improves cardiac function in heart failure after myocardial infarction (MI). Rabbits with heart failure induced by MI and sham-operated animals were randomized to orally receive apocynin, an inhibitor of NADPH oxidase (15 mg per day) or placebo for 4 weeks. Left ventricular (LV) dimension and function were assessed by echocardiography and hemodynamics. Myocardial NADPH oxidase activity was measured by superoxide dismutase-inhibitable cytochrome c reduction assay, NADPH oxidase subunit p47phox expression by Western blot and immunofluorescence analysis, myocardial oxidative stress evaluated by 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal (4-HNE) using immunohistochemistry, and myocyte apoptosis by TUNEL assay. MI rabbits exhibited LV dilatation and systolic dysfunction measured by LV fractional shortening and the maximal rate of LV pressure rise (dP/dt). These changes were associated with increases in NADPH oxidase activity, p47phox protein expression, 8-OHdG expression, 4-HNE expression, myocyte apoptosis, and Bax protein and a decrease in Bcl-2 protein. Apocynin reduced NADPH oxidase activity, p47phox protein, oxidative stress, myocyte apoptosis, and Bax protein, increased Bcl-2 protein, and ameliorated LV dilatation and dysfunction after MI. The results suggest that inhibition of NADPH oxidase may represent an attractive therapeutic approach to treat heart failure.
Authors:
Fuzhong Qin; Megan Simeone; Ravish Patel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-04-29
Journal Detail:
Title:  Free radical biology & medicine     Volume:  43     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-02     Completed Date:  2007-10-31     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  271-81     Citation Subset:  IM    
Affiliation:
Cardiology Unit, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA. fqin@bu.edu
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MeSH Terms
Descriptor/Qualifier:
Acetophenones / therapeutic use*
Animals
Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
Apoptosis
Blood Pressure
Disease Models, Animal
Enzyme Inhibitors / therapeutic use*
Heart / physiology*
Heart Failure / drug therapy*
Humans
Myocardial Infarction / drug therapy*
Myocardium / cytology,  enzymology*,  metabolism
Myocytes, Cardiac / pathology
NADPH Oxidase / antagonists & inhibitors*,  metabolism
Organ Size
Oxidative Stress / physiology*
Rabbits
Reactive Oxygen Species / metabolism
Chemical
Reg. No./Substance:
0/Acetophenones; 0/Anti-Inflammatory Agents, Non-Steroidal; 0/Enzyme Inhibitors; 0/Reactive Oxygen Species; 498-02-2/acetovanillone; EC 1.6.3.1/NADPH Oxidase; EC 1.6.3.1/neutrophil cytosolic factor 1

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