Neuregulin-1 attenuates mitochondrial dysfunction in a rat model of heart failure / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 807-814, 2012.
Article
in En
| WPRIM
| ID: wpr-262521
Responsible library:
WPRO
ABSTRACT
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>
Full text:
1
Index:
WPRIM
Main subject:
Pathology
/
Echocardiography
/
Blotting, Western
/
Reactive Oxygen Species
/
Rats, Wistar
/
Apoptosis
/
Neuregulin-1
/
Therapeutic Uses
/
Drug Therapy
/
Real-Time Polymerase Chain Reaction
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Chinese Medical Journal
Year:
2012
Type:
Article