The impact of high-salt exposure on cardiovascular development in the early chick embryo.
In this study, we show that high-salt exposure dramatically increases chick mortality during embryo development. As embryonic mortality at early stages mainly results from defects in cardiovascular development, we focused on heart formation and angiogenesis. We found that high-salt exposure enhanced the risk of abnormal heart tube looping and blood congestion in the heart chamber. In the presence of high salt, both ventricular cell proliferation and apoptosis increased. The high osmolarity induced by high salt in the ventricular cardiomyocytes resulted in incomplete differentiation, which might be due to reduced expression of Nkx2.5 and GATA4. Blood vessel density and diameter were suppressed by exposure to high salt in both the yolk sac membrane (YSM) and chorioallantoic membrane models. In addition, high-salt-induced suppression of angiogenesis occurred even at the vasculogenesis stage, as blood island formation was also inhibited by high-salt exposure. At the same time, cell proliferation was repressed and cell apoptosis was enhanced by high-salt exposure in YSM tissue. Moreover, the reduction in expression of HIF2 and FGF2 genes might cause high-salt-suppressed angiogenesis. Interestingly, we show that high-salt exposure causes excess generation of reactive oxygen species (ROS) in the heart and YSM tissues, which could be partially rescued through the addition of antioxidants. In total, our study suggests that excess generation of ROS might play an important role in high-salt-induced defects in heart and angiogenesis.
Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632, China.
Guang
G
Wang
Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632, China.
Nuan
N
Zhang
Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632, China.
Yi-Fan
YF
Wei
Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632, China.
Yi-Mei
YM
Jin
Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632, China.
Shi-Yao
SY
Zhang
Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632, China.
Xin
X
Cheng
Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632, China.
Zheng-Lai
ZL
Ma
Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632, China.
Shu-Zhu
SZ
Zhao
Department of Neonates, The first Affiliated Hospital of Jinan University, Guangzhou 510632, China.
You-Peng
YP
Chen
Division of Cell and Developmental Biology, University of Dundee, Dundee DD1 5EH, UK.
Manli
M
Chuai
Department of Neonates, The first Affiliated Hospital of Jinan University, Guangzhou 510632, China Humboldt University of Berlin, University Hospital Charité, Center for Cardiovascular Research & Institute for Pharmacology, Hessischestrasse 3-4, Berlin D-10115, Germany yang_xuesong@126.com berthold.hocher@charite.de.
Berthold
B
Hocher
Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632, China Institute of Fetal-Preterm Labor Medicine, Jinan University, Guangzhou 510632, China yang_xuesong@126.com berthold.hocher@charite.de.
Xuesong
X
Yang
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D018376:Cardiovascular Abnormalities / Q000139:chemically induced* / Q000196:embryology; D049109:Cell Proliferation; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009024:Morphogenesis; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology*; D015017:Yolk Sac / Q000098:blood supply / Q000187:drug effects
D000975:Antioxidants; D017382:Reactive Oxygen Species; D012965:Sodium Chloride
Angiogenesis; Heart formation; High salt/osmolarity; ROS