Document Detail


Neuregulin-1/ErbB signaling and chronic heart failure.
MedLine Citation:
PMID:  20933198     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neuregulin-1 (NRG-1), a cardioactive growth factor released from endothelial cells, is indispensable for cardiac development, structural maintenance, and functional integrity of the heart. In recent years, a growing number of studies have focused on NRG-1 and members of the ErbB family that serve as receptors for NRG-1 in order to better understand the role of this signaling pathway in physiology and pathophysiology of the heart. An essential role for NRG-1 and ErbB in heart development and functionality has been suggested by studies in conditional NRG-1/ErbB-deficient mice and by the cardiac-related side effects of anti-ErbB2 antibody therapies used for treatment of breast cancer. In vitro and in vivo studies using recombinant human neuregulin-1 (rhNRG-1), which contains the epidermal growth factor (EGF)-like domain (necessary for ErbB2/ErbB4 activation), have further supported the hypothesis that NRG-1 plays an important role in heart function. Consistent with other studies, expression of rhNRG-1 not only restored normal cardiomyocytic structure altered by nutritional deficiency in cell cultures, but also improved the pumping function of the heart in several animal models of chronic heart failure (CHF). As a result of these findings, proteins involved in the NRG-1/ErbB-signaling pathway have been explored as potential drug targets for treatment of heart failure. Clinical trials to evaluate the safety and efficacy of rhNRG-1 have been conducted in both China and Australia. As predicted, rhNRG-1 treatment improved both cardiac function and reversed remodeling of the heart. Therefore, rhNRG-1 may represent a new drug for treatment of CHF with a novel therapeutic mechanism.
Authors:
Yabei Xu; Xinyan Li; Xifu Liu; Mingdong Zhou
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Advances in pharmacology (San Diego, Calif.)     Volume:  59     ISSN:  1557-8925     ISO Abbreviation:  Adv. Pharmacol.     Publication Date:  2010  
Date Detail:
Created Date:  2010-10-11     Completed Date:  2010-11-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9015397     Medline TA:  Adv Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  31-51     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Zensun Science and Technology Co. Ltd., Shanghai, China.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Animals
Clinical Trials as Topic
Disease Models, Animal
Drug Design*
Heart / anatomy & histology,  physiology
Heart Failure / drug therapy,  metabolism*,  pathology
Humans
Middle Aged
Neuregulin-1* / adverse effects,  physiology,  therapeutic use
Receptor, Fibroblast Growth Factor, Type 4 / physiology
Receptor, erbB-2 / physiology
Recombinant Proteins / therapeutic use
Signal Transduction / physiology
Young Adult
Chemical
Reg. No./Substance:
0/Neuregulin-1; 0/Recombinant Proteins; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 4; EC 2.7.10.1/Receptor, erbB-2

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