Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-13694-5
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Funding
- National Key R&D Program of China [2017YFA0103700]
- National Natural Science Foundation of China [31571528]
- National Natural Science Foundation of Zhejiang Province [LR15H020001]
- Recruitment Program of Global Experts of the Organization Department of the Central Committee of the CPC
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Cadmium (Cd) is a harmful heavy metal that results in vascular diseases such as atherosclerosis. Prior evidence revealed that Cd induced endothelial cell (EC) death and dysfunction, supporting that ECs are a primary target of Cd-induced toxicity, and can cause severe pathologies of vascular diseases. However, the underlying mechanisms remain unclear. In this study, we investigated the mechanisms of Cd-induced endothelial toxicity in a human model system of H9 human pluripotent stem cell-derived endothelial cells (H9-ECs). We showed that H9-ECs were susceptible to CdCl2 induction, leading to detrimental changes of cell structure and significantly elevated level of apoptosis. We demonstrated that CdCl2-treated H9-ECs gave rise to a clear EC dysfunction phenotype and significantly differential transcriptomic profile. Signaling pathway analysis revealed that P38 or ERK signaling pathway is critical to cadmium-induced EC apoptosis and dysfunction, and inhibition of P38 or ERK effectively rescued CdCl2-induced endothelial toxicity in H9-ECs. Conclusively, hPSC-ECs can be a reliable model to recapitulate the EC pathological features and transcriptomic profile, which may provide a unique platform for understanding the cellular and molecular mechanisms of Cd-induced endothelial toxicity and for identifying therapeutic drugs for Cd-induced vascular diseases.
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