TNF and endothelial dysfunction: In contrast with the insults elicited by Ang II and CRP, the TNF-α induced oxidative stress and endothelial dysfunction are associated with the activation of ceramide-induced activation of JNK and subsequent production of superoxide via xanthine oxidase (77, 98) rather than the signaling via p38 MAPK-activated NAD(P)H oxidase (49, 78).