Modelling cadmium-induced cardiotoxicity using human pluripotent stem cell-derived cardiomyocytes.
Modelling cadmium-induced cardiotoxicity using human pluripotent stem cell-derived cardiomyocytes.
J Cell Mol Med. 2018 Jul 11;:
Authors: Shen J, Wang X, Zhou D, Li T, Tang L, Gong T, Su J, Liang P
Abstract
Cadmium, a highly ubiquitous toxic heavy metal, has been widely recognized as an environmental and industrial pollutant, which confers serious threats to human health. The molecular mechanisms of the cadmium-induced cardiotoxicity (CIC) have not been studied in human cardiomyocytes at the cellular level. Here we showed that human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) can recapitulate the CIC at the cellular level. The cadmium-treated hPSC-CMs exhibited cellular phenotype including reduced cell viability, increased apoptosis, cardiac sarcomeric disorganization, elevated reactive oxygen species, altered action potential profile and cardiac arrhythmias. RNA-sequencing analysis revealed a differential transcriptome profile and activated MAPK signalling pathway in cadmium-treated hPSC-CMs, and suppression of P38 MAPK but not ERK MAPK or JNK MAPK rescued CIC phenotype. We further identified that suppression of PI3K/Akt signalling pathway is sufficient to reverse the CIC phenotype, which may play an important role in CIC. Taken together, our data indicate that hPSC-CMs can serve as a suitable model for the exploration of molecular mechanisms underlying CIC and for the discovery of CIC cardioprotective drugs.
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Source: J Cell Mol Med - Category: Molecular Biology Authors: Shen J, Wang X, Zhou D, Li T, Tang L, Gong T, Su J, Liang P Tags: J Cell Mol Med Source Type: research
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