title: Excess ROS induced by AAPH causes myocardial hypertrophy in the developing chick embryo.
abstract: 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.
  
  
  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.affiliation: Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Zhao-long
authors.initials: ZL
authors.lastname: Zhang
authors.affiliation: Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Pharmacy College, Jinan University, Guangzhou 510632, China.
authors.forename: Xiao-Di
authors.initials: XD
authors.lastname: Li
authors.affiliation: Division of Cell and Developmental Biology, University of Dundee, Dundee, DD1 5EH, UK.
authors.forename: Manli
authors.initials: M
authors.lastname: Chuai
authors.affiliation: Key Laboratory for Regenerative Medicine of the Ministry of Education, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Kenneth Ka Ho
authors.initials: KK
authors.lastname: Lee
authors.affiliation: Pharmacy College, Jinan University, Guangzhou 510632, China.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurihara
authors.affiliation: Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China. Electronic address: yang_xuesong@126.com.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
mesh_terms: D000578:Amidines / Q000633:toxicity*; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000578:Amidines; D017382:Reactive Oxygen Species; C046728:2,2'-azobis(2-amidinopropane)
keywords: AAPH; Cardiomyocytes; Chick embryo; Hypertrophy; ROS