Document Detail


Neuregulin-1 attenuates mitochondrial dysfunction in a rat model of heart failure.
MedLine Citation:
PMID:  22490579     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: Mitochondrial dysfunction plays a pivotal role in the progression of left ventricular (LV) remodeling and heart failure (HF). Recombinant human neuregulin-1 (rhNRG-1) improves cardiac function in models of experimental HF and in clinical trials; however, its impact on mitochondrial function during chronic HF remains largely unknown. The purpose of this study was to investigate whether rhNRG-1 could attenuate the functional and structural changes that occur in cardiac mitochondria in a rat model of HF induced by myocardial infarction.
METHODS: Sixty adult rats underwent sham or coronary ligation to induce HF. Four weeks after ligation, 29 animals with LV ejective fraction ≤ 50% were randomized to receive either vehicle or rhNRG-1 (10 µg×kg(-1)×d(-1), I.V.) for 10 days, another 12 sham-operated animals were given no treatment. Echocardiography was used to determine physiological changes. Mitochondrial membrane potential (MMP), respiratory function and tissue adenosine triphosphate (ATP) production were analyzed. Cytochrome c expression and cardiomyocyte apoptosis were determined. Oxidative stress was evaluated by reactive oxygen species production using fluorescence assays and gene expression of glutathione peroxidase measured by real-time quantitative PCR.
RESULTS: Compared with sham-operated animals, vehicle treated HF rats exhibited severe LV remodeling and dysfunction, significant mitochondrial dysfunction, increased mitochondrial cytochrome c release, increased myocyte apoptosis and enhanced oxidative stress. Short-term treatment with rhNRG-1 significantly attenuated LV remodeling and cardiac function. Concomitant with this change, mitochondrial dysfunction was significantly attenuated; with ATP production, MMP and respiratory function restored, cytochrome c release and apoptosis inhibited, and oxidative stress reduced.
CONCLUSION: The present study demonstrated that rhNRG-1 can significantly improve LV remodeling and cardiac function in the failing heart, this beneficial effect is related to reducing mitochondrial dysfunction, myocyte apoptosis and oxidative stress.
Authors:
Yong-Fang Guo; Xiao-Xia Zhang; Yong Liu; Hong-Yan Duan; Bing-Zhang Jie; Xue-Si Wu
Related Documents :
22902709 - The role of nitric oxide, reactive oxygen species, and protein kinase c in oxytocin-ind...
20122549 - Pump failure death and sudden cardiac death in patients with cardiac dysfunction: a sea...
933409 - Sudden cardiac death: a retrospective and prospective study.
12142109 - Long-term clinical significance of frequent and complex ventricular tachyarrhythmias in...
6686529 - Hypertrophic cardiomyopathy: a common cause of sudden death in the young competitive at...
3732099 - Potassium loss, ventricular irritability, and the risk of sudden death in hypertensive ...
10552089 - Noninvasive determination of myocardial blood flow, oxygen consumption and efficiency i...
9710689 - The variable morphological coexistence of apoptosis and necrosis in human myocardial in...
22336189 - Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarc...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chinese medical journal     Volume:  125     ISSN:  0366-6999     ISO Abbreviation:  Chin. Med. J.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-04-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7513795     Medline TA:  Chin Med J (Engl)     Country:  China    
Other Details:
Languages:  eng     Pagination:  807-14     Citation Subset:  IM    
Affiliation:
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Fatty acid desaturase 1 polymorphisms are associated with coronary heart disease in a Chinese popula...
Next Document:  Effect of metoprolol on sarcoplasmic reticulum Ca2+ leak in a rabbit model of heart failure.