It is more likely to be a secondary ionotropic receptor downstream of a Ca2+-permeable mechanosensitive ion channel, such as Piezo1 (Gnanasambandam et al., 2015; Syeda et al., 2016) or TRPV2/4 (Lieben and Carmeliet, 2012), that functions as the primary mechanoreceptor responding directly to pressure overload and thus initiating the hypertrophic response in TAC, which is not dependent on activation of the calcineurin-NFAT pathway (Yu et al., 2021). This evidence concerns the gene PIEZO1 and persistent truncus arteriosus.