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conferenceseries
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Volume 4
Toxicology: Open Access
ISSN: 2476-2067
Toxicology Congress 2018
March 12-14, 2018
March 12-14, 2018 Singapore
14
th
World Congress on
Toxicology and Pharmacology
Tobacco smoking-induced toxicity in cardiomyocytes derived from human pluripotent stem cells
Maocheng Yang
1
, Xi Yang
2
and Matthew C White
1
1
Center for Tobacco Products, USA
2
National Center for Toxicological Research, USA
C
igarette smoking is an important risk factor for heart disease. Mechanistically-relevant biomarkers could provide timely
assessment of the toxicity of tobacco products, including new products that wish to make claims with reduced health risks.
The goal of this study is to investigate toxic effects and identify biomarkers of harm in induced pluripotent stem cell (iPSC)-
derived human cardiomyocytes. Two cigarette smoke condensate (CSC) concentrations were tested: Low (10 µg/ml) and high
(30 µg/ml) following 1-30 day exposures. RNA was isolated at defined time points (1, 7, 14, 30 days) and global gene expression
was analyzed using next-generation sequencing. Exposure of cardiomyocytes to CSCs resulted in significant changes tomultiple
transcripts. The Nrf2-mediated oxidative stress pathway was consistently up-regulated across all time points. Moreover,
microRNA-34a, which is involved in the regulation of Nrf2, was down-regulated (two-fold) in CSC-treated cardiomyocytes
as early as 24 hours. The high concentration caused the largest reduction in cell viability at the longest exposure time (30
days). Interestingly, induction of the DNA damage and repair pathways occurred only after 30-day exposure .Transcriptional
regulation of the Nrf2 pathway may be involved in the underlying mechanism associated with smoking-induced cardio-
toxicity. Significantly dysregulated transcripts, such as heme oxygenase 1, glutathione S-reductase and microRNA-34a, in this
pathway are potential biomarkers of harm that may be useful as surrogate markers in epidemiological studies and clinical trials
to evaluate new tobacco products.
maocheng.yang@fda.hhs.govToxicol Open Access 2018, Volume 4
DOI: 10.4172/2476-2067-C1-006