Effects of cigarette smoke components on myocardial differentiation of mouse embryonic stem cells

• Published in: Environmental toxicology 2020-01, Vol.35 (1), p.66-77
• Main Authors: Kim, Cho‐Won, Go, Ryeo‐Eun, Ko, Eul Bee, Jeung, Eui‐Bae, Kim, Min‐Seok, Choi, Kyung‐Chul
• Format: Article
• Language: English
• Subjects: Animals; Calcium-binding protein; cardiomyocyte; Cardiomyocytes; cell cycle; Cell Cycle - drug effects; Cell differentiation; Cell Differentiation - drug effects; Cigarette smoke; cigarette smoke extract; Cigarettes; Components; Cyclin D1; Cyclin D1 - metabolism; D1 protein; Differentiation; Embryo cells; Exposure; Fetuses; Foetus; GTP-binding protein; HDAC2 protein; HDACs; Heart; Histone deacetylase; Histone Deacetylase 2 - metabolism; Mice; mouse embryonic stem cells; Mouse Embryonic Stem Cells - cytology; Mouse Embryonic Stem Cells - drug effects; Mouse Embryonic Stem Cells - metabolism; myocardial differentiation; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Nicotiana - toxicity; Nicotine; p53 Protein; Signal Transduction - drug effects; Smoke; Smoke - adverse effects; Smoking - adverse effects; Stem cell transplantation; Stem cells; Tobacco smoke; Troponin; Troponin I
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.22843

The heart is the first organ formed in the developing fetus, and abnormal development of the heart is a major cause of fetal death. The adverse effects of cigarette smoke on the heart have been well established, but it is not well understood how cigarette smoke components regulate signaling molecules and cardiac specific functions during the early differentiation stage of the embryonic heart. In this study, we identified changes in the size of mouse embryoid bodies (mEBs) in response to treatment with cigarette smoke extract (CSE) via regulation of HDAC2, p53, p21, and cyclin D1 protein expression, which are cardiac differentiation and cell‐cycle markers, respectively. In addition, exposure of mouse embryonic stem cells (mESCs) to cigarette smoke components inhibited myocardial differentiation and development through the expression of HDAC1, HDAC2, GATA4, NKX2‐5, TBX5, HAND1, and Troponin I. Long‐term exposure studies showed that CSE and nicotine may delay the development of mouse cardiomyocytes from mESCs and inhibit the contractibility, which is a fundamental function of the heart. Taken together, these findings suggest that cigarette smoke components, including nicotine, may affect abnormal myocardial differentiation and development.