Epicardium Formation as a Sensor in Toxicology

Abstract

Zebrafish (Danio rerio) are an excellent vertebrate model for studying heart development, regeneration and cardiotoxicity. Zebrafish embryos exposed during the temporal window of epicardium development to the aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exhibit severe heart malformations. TCDD exposure prevents both proepicardial organ (PE) and epicardium development. Exposure later in development, after the epicardium has formed, does not produce cardiac toxicity. It is not until the adult zebrafish heart is stimulated to regenerate does TCDD again cause detrimental effects. TCDD exposure prior to ventricular resection prevents cardiac regeneration. It is likely that TCDD-induced inhibition of epicardium development and cardiac regeneration occur via a common mechanism. Here, we describe experiments that focus on the epicardium as a target and sensor of zebrafish heart toxicity.

Cardiac Development in Zebrafish and Human Embryonic Stem Cells Is Inhibited by Exposure to Tobacco Cigarettes and E-Cigarettes

“…The finding that nicotine treatment alone recapitulated untreated controls indicates that the impact of e-cigarette and tobacco cigarette on heart development is the consequence of other components. Many chemicals, including known ingredients in tobacco cigarettes such as polycyclic aromatic hydrocarbons can cause gross morphological defects [ 43 – 46 ]. Reports have also shown significant toxicity from e-cigarette treatment [ 12 , 13 , 47 ] with some reports showing the cause to be the presence of cinnamaldehyde and 2-methoxycinamaldehyde in e-cigarette flavorings [ 48 , 49 ], the presence of formaldehyde in e-cigarette vapor[ 50 ], and tin particles in cartomizer fluid [ 51 ].…”

Transcription Factor 21: A Transcription Factor That Plays an Important Role in Cardiovascular Disease

“…TCF21 promotes the expression of AHR heterodimer partner ARNT AHR and cooperates with these factors to upregulate some inflammatory downstream disease-related genes, including IL1A, MMP1, and CYP1A1. TCF21 binds to AHR, ARNT, and downstream target gene loci, and the binding sites of AHR-ARNT and TCF21 are colocated throughout the genome of HCASMC open chromatin region [84]. These co-localization regions were found to be enriched with GWAS signals associated with cardiac metabolism and chronic inflammatory disease phenotypes.…”

Research progress in cardiotoxicity of organophosphate esters

“…Conversely, excessive activation of AHR can mediate inflammatory responses, leading to atherosclerosis in mice (Wu et al, 2011). It has been found that 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD) can inhibit epicardial formation during cardiac development by activating the AHR pathway, resulting in developmental malformations, volume reduction, decreased cardiomyocyte numbers, blood regurgitation, and conduction block in the heart (Antkiewicz et al, 2005;Hofsteen et al, 2013). TCDD-like compounds and polycyclic aromatic hydrocarbons (PAHs) are the two main types of environmental pollutants known to activate the AHR signaling pathway.…”