TNF and ischemia: Functionally, exRNA and TNF-α appear to act in a feed-forward loop to promote cardiac ischemia-reperfusion injury: the increase in exRNA leads to an accumulation of TNF-α, and in turn, TNF-α activation of adjacent cells via TNF-receptor-1 provokes an increase in exRNA as well, resulting in a hyper-inflammatory situation (Cabrera-Fuentes et al., 2014).