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

Abstract

An association has been proved between high salt consumption and cardiovascular mortality. In vertebrates, the heart is the first functional organ to be formed. However, it is not clear whether high-salt exposure has an adverse impact on cardiogenesis. Here we report high-salt exposure inhibited basement membrane breakdown by affecting RhoA, thus disturbing the expression of Slug/E-cadherin/N-cadherin/Laminin and interfering with mesoderm formation during the epithelial-mesenchymal transition(EMT). Furthermore, the DiI cell migration trajectory in vivo and scratch wound assays in vitro indicated that high-salt exposure restricted cell migration of cardiac progenitors, which was caused by the weaker cytoskeleton structure and unaltered corresponding adhesion junctions at HH7. Besides, down-regulation of GATA4/5/6, Nkx2.5, TBX5, and Mef2c and up-regulation of Wnt3a/β-catenin caused aberrant cardiomyocyte differentiation at HH7 and HH10. High-salt exposure also inhibited cell proliferation and promoted apoptosis. Most importantly, our study revealed that excessive reactive oxygen species(ROS)generated by high salt disturbed the expression of cardiac-related genes, detrimentally affecting the above process including EMT, cell migration, differentiation, cell proliferation and apoptosis, which is the major cause of malformation of heart tubes.

Comprehensive analysis of EMT-related genes and lncRNAs in the prognosis, immunity, and drug treatment of colorectal cancer

“…The role of TBX5 in the EMT process is mainly to initiate the formation of mesenchymal limb progenitors [ 20 ]. Up-regulation of TBX5 promotes the formation of mesoderm during EMT and affects the differentiation of cardiomyocytes [ 21 ]. The increase of TBX5 drives the mesenchymal phenotype of breast cancer, promotes the EMT process, and inhibits the expression of the immune response network [ 22 ].…”

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“…Since migration of human dermal fibroblasts is critical for wound contraction and repair, our results indicate that increased sodium concentration may impair the motility of DFs, which can disturb wound repair mechanisms. Furthermore, these results are in accordance with previous observations demonstrating reduced migratory capacity of myocardial and endothelial cells in high salt condition [54,55].…”

Association of Maternal Dietary Habits and Infant MTHFR Gene Polymorphisms with Ventricular Septal Defect in Offspring: A Case–Control Study

“…The strongest association (OR = 5.89) was observed between maternal frequent consumption of corned foods (≥6 times per week) during the first trimester and VSD in offspring. This may be attributed to the excessive intake of sodium when consuming corned foods since high-salt-induced reactive oxygen species interfered with the migration of cardiac progenitor cells and their gene expression [34]. Our findings demonstrated the adverse impact of fermented bean curd intake on heart defects in offspring (3-5 times per week: OR = 1.70; ≥6 times per week: OR = 4.50).…”