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Excess ROS induced by AAPH causes myocardial hypertrophy in the developing chick embryo.
MedLine Citation:
PMID:  25037699     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: The developing embryo is very sensitive to oxidative stress and excess reactive oxygen species (ROS) generation is often associated with cardiovascular malformation. However, little is known about the adverse effects of ROS during heart morphogenesis, especially during the formation of the atria and ventricles.
METHODS AND RESULTS: We have treated early chick embryos with 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH) to generate free radicals in the developing heart. We established that excess ROS induced by AAPH caused cardiomegaly to develop in 4-, 14- and 17-day-old embryos. The cardiomyocytes of these AAPH-treated hearts were hypertrophic, in both the compact and trabeculated myocardium. The weight of these hearts was also significantly increased in an AAPH dose-dependent fashion. We examined and compared the functions of the AAPH-treated and untreated hearts by echocardiography and determined that the ejection fraction was shortened. BrdU incorporation assay was performed and revealed that cell proliferation was not the main cause of cardiomegaly. However, we established that the cardiomyocytes exposed to excess ROS were distinctively larger than control cardiomyocytes - indicting that cardiomegaly was attributed to hypertrophy. We have also found that excess ROS inhibited Wnt signaling but enhanced VEGF signaling. Consequently, this promoted angiogenesis and caused larger coronary arteries to develop in the AAPH-treated hearts.
CONCLUSIONS: We have demonstrated that cardiomyocyte hypertrophy and changes in Wnt and VEGF signaling were the main contributing factors in the development of cardiomegaly induced by oxidative stress.
Authors:
Yan Li; Xiao-Yu Wang; Zhao-Long Zhang; Xin Cheng; Xiao-Di Li; Manli Chuai; Kenneth Ka Ho Lee; Hiroshi Kurihara; Xuesong Yang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-2
Journal Detail:
Title:  International journal of cardiology     Volume:  -     ISSN:  1874-1754     ISO Abbreviation:  Int. J. Cardiol.     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-7-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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