Improvement of cardiac function and reversal of gap junction remodeling by Neuregulin-1β in volume-overloaded rats with heart failure

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Author:
Xue-Hui Wang(Department of Cardiovascular Medicine, the First Affiliated Hospital of Medical School, Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China;Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China;Department of Cardiovascular Medicine, First Hospital of Xinxiang Medical)
Xiao-Zhen Zhuo(Department of Cardiovascular Medicine, the First Affiliated Hospital of Medical School, Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China;Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China)
Ya-Juan Ni(Department of Cardiovascular Medicine, the First Affiliated Hospital of Medical School, Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China;Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China)
Min Gong(Department of Cardiovascular Medicine, the First Affiliated Hospital of Medical School, Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China;Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China)
Ting-Zhong Wang(Department of Cardiovascular Medicine, the First Affiliated Hospital of Medical School, Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China;Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China)
Qun Lu(Department of Cardiovascular Medicine, the First Affiliated Hospital of Medical School, Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China;Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China)
Ai-Qun Ma(Department of Cardiovascular Medicine, the First Affiliated Hospital of Medical School, Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an 710061, Shaanxi Province, China;Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China)
Journal Title:
JOURNAL OF GERIATRIC CARDIOLOGY
Issue:
Volume 09, Issue 02, 2012
DOI:
10.3724/SP.J.1263.2012.03271
Key Word:
Neuregulin-1β;Cardiac function;Heart failure;Connexin 43;Gap junction;Remodeling

Abstract: Objective We performed experiments using Neuregulin-1β (NRG-1β) treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions (GJs) during heart failure (HF). Methods Rat models of HF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF (HF, n = 16), NRG-1β treatment (NRG, n = 16), and sham operation (S, n = 16) group. The rats in the NRG group were administered NRG-1β (10 μg/kg per day) for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline. Twelve weeks after operation, Connexin 43 (Cx43) expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastructure of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac function of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastructure of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.

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