Caveolin-1 (Cav-1) regulates the functions of different NOS isoforms, and Nakamura [58] previously found a lower expression level of Cav-1 in the colon of patients with HSCR, which led them to speculate that reduced Cav-1 expression may lead to excessive activation of iNOS, consequently leading to epithelial damage and thus increasing the susceptibility of HSCR to HAEC. This evidence concerns the gene NOS2 and Hirschsprung disease.