Further, recent work by authors of the present report and others, demonstrate that melanocortins protect against tissue damage in response to prolonged myocardial ischemia/reperfusion via activation of pro-survival HO-1 protein, JAK/ERK/STAT signalling and decreased expression of the pro-inflammatory mediator TNF-α and pro-inflammatory/pro-apoptotic factor pJNK and also by vagus nerve-mediated cholinergic anti-inflammatory pathway [46,57,58]. Here, TNF is linked to myocardial ischemia.