Proposed schematic representation of the signaling pathways leading to atorvastatin-induced cardioprotection of the human myocardium, in vitro. Continuous administration of atorvastatin during hypoxia-reoxygenation induced tumor necrosis factor (TNF)-α activation, phosphorylation/activation of signal transducers and activators of transcription (STAT)-3 and Janus kinase (JAK)-2, and the inhibition of mitochondrial permeability transition pore (mPTP) mediate the cardioprotective effect. In atorvastatin-induced cardioprotection, TNF-α activation occurred before and could trigger the JAK-2 and STAT-3 activation/phosphorylation; and inhibition of mPTP opening appears to be downstream of activation of TNF-α, JAK-2, and STAT-3.