The impact of high salt exposure on cardiovascular development in the early chick embryo

Abstract

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-saltsuppressed 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-saltinduced defects in heart and angiogenesis.

High salt‐induced excess reactive oxygen species production resulted in heart tube malformation during gastrulation

“…In our previous, we have found that excess ROS affected cell proliferation, as well as apoptosis and resulted in embryonic cardiovascular dysplasia (Wang et al, ). To further explore whether the influence of excess ROS on proliferation and apoptosis, we employed the H9c2 cells cultured in vitro in presence of high salt.…”

“…For the Vitamin C (VC) −treated embryos, the HH0, HH4, or HH7 chick embryos in EC culture were incubated with 2.86 mM VC (Beijing Ding Guo Chang Sheng, China) according to experimental requirements. Chick embryo treatment of VC is 0.5 mg/egg (Li et al, ; Wang et al, ). In EC‐culture, it is 1 ml/embryo, so the final concentration is 2.86 mM (=0.5 mg/ml) in culture medium.…”

VEGF‐C attenuates renal damage in salt‐sensitive hypertension

“…High salt has been shown to increase the production of reactive oxygen species leading to impaired nitric oxide signaling, arterial stiffening, and vasoconstriction (Banday, Muhammad, Fazili, & Lokhandwala, ; Bayorh, Ganafa, Socci, Silvestrov, & Abukhalaf, ; Dobrian et al, ; Trolliet, Rudd, & Loscalzo, ). In hypertensive models with enhanced oxidative stress such as in high‐salt induced hypertension, renal expression of SOD has been found to be increased to cope with the increase in superoxide production (Sainz et al, ; Vaziri, Lin, Farmand, & Sindhu, ; Y. Wang, Chen, & Wang, ; G. Wang et al, ). Herein, high‐salt diet induced an increase in the expression of CuZn‐SOD and Mn‐SOD that was concomitant with the increase of urinary RNA/DNA damage markers.…”

Growth and cardiovascular development are repressed by florfenicol exposure in early chicken embryos

“…The cardiovascular system is the first system to emerge during embryonic development and plays critical roles in the distribution of blood to various tissues to fulfill oxygen and nutrient requirements. This system is composed of the heart and the vascular system, which are derived from the embryonic mesoderm and extraembryonic yolk sac ( Wang et al., 2015a ). The formation of the heart is a complex morphogenetic process that depends on the spatiotemporally regulated contribution of cardiac progenitor cells ( Vincent and Buckingham, 2010 ).…”