Ischemia/reperfusion injury and cardioprotective mechanisms: Role of mitochondria and reactive oxygen species

Figure 2 Flowchart depicting the main factors involved in cardioprotective pathways triggered by pre and postconditioning. Activation of cell-surface receptors in response to an ischaemic conditioning stimulus recruits cGMP/PKG, RISK and SAFE pathways. In particular, iNOS seems to be involved in SAFE pathway[77]. These signal transduction pathways, together with acidosis, activated at the time of reperfusion will crosstalk and will terminate on mitochondria to activate protective pathways. Akt: Serine/threonine protein kinase; cGMP/PKG: Cyclic guanosin monophosphate/protein kinase G; eNOS: Endothelial NO synthase; ERK1/2: Extracellular regulated kinase 1/2; gp130: Glycoprotein 130; GPCR: G-protein-coupled receptor; GSK3β: Glycogen synthase kinase 3 β; IL-6: Interleukin 6; iNOS: Inducible NO synthase; JAK: Janus kinase; MEK: Mitogen-activated protein kinase kinase; mPTP: Mitochondrial permeability transition pore; NO: Nitric oxide; P70S6K: p70 ribosomal S6 protein kinase; PI3K: Phosphoinositide 3-kinase; PKG: Protein kinase G; RISK: Reperfusion injury salvage kinases; SAFE: Survivor activating factor enhancement; STAT-3: Signal transducer and activator of transcription 3; TNFα: Tumour necrosis factor α; TNF-R2: Tumour necrosis factor receptor 2.