Open AccessModelling cadmium‐induced cardiotoxicity using human pluripotent stem cell‐derived cardiomyocytes
Author(s) -
Shen Jiaxi,
Wang Xiaochen,
Zhou Danni,
Li Tongyu,
Tang Ling,
Gong Tingyu,
Su Jun,
Liang Ping
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13702
Subject(s) - induced pluripotent stem cell , mapk/erk pathway , cardiotoxicity , microbiology and biotechnology , phenotype , pi3k/akt/mtor pathway , transcriptome , cadmium , apoptosis , biology , protein kinase b , chemistry , cancer research , signal transduction , embryonic stem cell , biochemistry , genetics , gene expression , gene , organic chemistry , chemotherapy
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 ‐ CM s) can recapitulate the CIC at the cellular level. The cadmium‐treated hPSC ‐ CM s 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 ‐ CM s, and suppression of P38 MAPK but not ERK MAPK or JNK MAPK rescued CIC phenotype. We further identified that suppression of PI 3K/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 ‐ CM s can serve as a suitable model for the exploration of molecular mechanisms underlying CIC and for the discovery of CIC cardioprotective drugs.