In this study, we showed that high salt exposure dramatically increased chick embryonic mortality during embryo development. As embryonic mortality at early stages mainly results from defects in cardiovascular development, we focused on heart formation and angiogenesis in the following experiments. 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 Nkx2.5 and GATA4 expression. Blood vessel density and diameter were suppressed by exposure to high salt in both the yolk sac membrane (YSM) and chorioallantoic membrane (CAM) 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 HIF2 and FGF2 gene expression might cause the high salt-suppressed angiogenesis. Interestingly, we showed that high salt exposure caused excess ROS generation in the heart and YSM tissues, which could be partially rescued through the addition of antioxidants. In total, our study suggested that excess ROS generation might play an important role in high-salt induced the heart and angiogenesis defects.
↵# Contributed to the work equally
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