Abstract

Chronic exposure to environmental pollutants threatens human health. Arsenic, a world-wide diffused toxicant, is associated to cardiac pathology in the adult and to congenital heart defects in the foetus. Poorly known are its effects on perinatal cardiomyocytes. Here, bioinformatic image-analysis tools were coupled with cellular and molecular analyses to obtain functional and structural quantitative metrics of the impairment induced by 0.1, 0.5 or 1.0 µM arsenic trioxide exposure on the perinatal-like cardiomyocyte component of mouse embryoid bodies, within their 3D complex cell organization. With this approach, we quantified alterations to the (a) beating activity; (b) sarcomere organization (texture, edge, repetitiveness, height and width of the Z bands); (c) cardiomyocyte size and shape; (d) volume occupied by cardiomyocytes within the EBs. Sarcomere organization and cell morphology impairment are paralleled by differential expression of sarcomeric α-actin and Tropomyosin proteins and of acta2, myh6 and myh7 genes. Also, significant increase of Cx40, Cx43 and Cx45 connexin genes and of Cx43 protein expression profiles is paralleled by large Cx43 immunofluorescence signals. These results provide new insights into the role of arsenic in impairing cytoskeletal components of perinatal-like cardiomyocytes which, in turn, affect cell size, shape and beating capacity.

Highlights

  • Chronic exposure to environmental pollutants threatens human health

  • The kinematic and dynamic cardiomyocyte features determined in a previous work of o­ urs[27], i.e. the chronotropy, dynamic inotropy, kinematic inotropy, and ergotropy, were evaluated for comparison between untreated (CTR) and arsenic trioxide (ATO)-exposed samples

  • Making use of a mouse embryonic stem cells (mESCs) differentiation platform, the aim of this study was to investigate the detrimental effects of ATO on the perinatal-like cardiomyocyte component of the embryoid bodies (EBs), with a focus on cell organization and function

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Summary

Introduction

Chronic exposure to environmental pollutants threatens human health. Arsenic, a world-wide diffused toxicant, is associated to cardiac pathology in the adult and to congenital heart defects in the foetus. Bioinformatic image-analysis tools were coupled with cellular and molecular analyses to obtain functional and structural quantitative metrics of the impairment induced by 0.1, 0.5 or 1.0 μM arsenic trioxide exposure on the perinatallike cardiomyocyte component of mouse embryoid bodies, within their 3D complex cell organization. With this approach, we quantified alterations to the (a) beating activity; (b) sarcomere organization (texture, edge, repetitiveness, height and width of the Z bands); (c) cardiomyocyte size and shape; (d) volume occupied by cardiomyocytes within the EBs. Sarcomere organization and cell morphology impairment are paralleled by differential expression of sarcomeric α-actin and Tropomyosin proteins and of acta[2], myh[6] and myh[7] genes. At the end of differentiation, the electrophysiological characteristics, sarcomere protein expression and ion channel expression of mESC-derived cardiomyocytes are reminiscent of embryonic and postnatal murine c­ ardiomyocytes[17,22,23,24]

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