Excess ROS induced by AAPH causes myocardial hypertrophy in the developing chick embryo

Yan Li, Xiao-Yu Wang, Zhao-long Zhang, Xin Cheng, Xiao-Di Li, Manli Chuai, Kenneth Ka Ho Lee, Hiroshi Kurihara, Xuesong Yang (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    32 Citations (Scopus)


    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.
    Original languageEnglish
    Pages (from-to)62-73
    Number of pages12
    JournalInternational Journal of Cardiology
    Issue number1
    Publication statusPublished - Sept 2014


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