EDN1 and endothelial dysfunction: The two promote each other through complex molecular mechanisms, such as pro-inflammatory factors (e.g., TNF-α and IL-6) that reduce NO production by inhibiting endothelial NO synthase while activating ET-1 release and oxidative stress products (e.g., malondialdehyde) that accelerate endothelial dysfunction through the degradation of NO, creating a vicious cycle of inflammation and endothelial damage (Gupta et al., 2020).