Figure 7
From: Cardiac spheroids as promising in vitro models to study the human heart microenvironment
Cross-talk between different cell types in DOX-induced cardiotoxicity. (a) DOX-induced effects on cardiomyocytes occurs via ROS/caspase 3-mediated apoptosis. (b) EC-released NO protects cardiomyocytes against DOX-induced toxicity. (c) DOX-induced eNOS up-regulation in endothelial cells produces toxic NO species. (d) DOX-induced eNOS up-regulation in cardiac fibroblasts produces the majority of the toxic NO species. (e) DOX-induced cardiotoxic effects via ROS production in cardiac fibroblasts. At the molecular level, DOX/superoxide-induced apoptosis in cardiomyocytes can be either rescued by endothelial cell-released NO, via inhibition of a ROS-mediated toxic effect, or can be exacerbated by increased eNOS expression and peroxynitrous acid formation. Cardiac fibroblasts can trigger DOX/NO-toxic effects by overexpressing eNOS and increasing peroxynitrous acid generation, or could increase superoxide levels and therefore feedback to endothelial cell-mediated peroxynitrous acid and cardiomyocyte apoptosis.
