Abstract
Ongoing cardiac remodeling can lead to negative outcomes, such as cardiac failure and diminished myocardial function, although the remodeling process initially protects the heart as a compensatory mechanism[1] . Importantly, ferroptosis appears to be a critical process in the development of cardiac disease. In a recent publication in Redox Biology, (Zhong et al. [2] showed that reactive oxygen species (ROS) generation and cardiac ferroptosis may be the mechanisms underlying angiotensin II (Ang II)-induced cardiac remodeling, as well as that ferroptosis is required for heart impairment and cardiac dysfunction induced by Ang II. Moreover, this study provides evidence that Ang II increases the expression of P2X7 receptors (P2X7R) in cardiac tissues and that both silencing and pharmacological inhibition of P2X7R significantly inhibited Ang II-induced ferroptosis and hypertrophy. Also, this work confirmed that P2X7R deficiency mitigated the Ang II-induced deterioration of cardiac injury in mice fed an iron-rich diet. Most interestingly, this study revealed that Ang II directly interacts with the P2X7R to activate and induce nucleocytoplasmic shuttling of human antigen R (HuR), which in turn controls the stability of the mRNA of heme oxygenase 1 (HO-1) and GPX4 and subsequent ROS production, which translated to induction of myocardial ferroptosis and remodeling.