Heme oxygenase-1 and heat shock proteins in ischemia/reperfusion injury

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Abstract
Purpose of review Ischemia/reperfusion injury is a multifactorial process that affects graft function after organ transplantation. The complex mechanism of IRI can be attributed to local neutrophil accumulation, release of proinflammatory mediators such as oxygen free radicals, and cytokines, which lead to cellular injury that culminates in the graft failure. This review examines the interlocked mechanisms of cellular protection rendered by heme oxygenase-1 and heat shock proteins during the course of ischemia/reperfusion injury in transplant recipients. Recent findings The heme oxygenase-1 and heat shock protein (HSP70) systems are among the most critical of cytoprotective mechanisms activated during cellular stress. The cytoprotection often seen in the transplanted organ after local heme oxygenase-1 overexpression may include several factors, such as antioxidant function, maintenance of microcirculation, antiapoptotic function, and antiinflammatory function. In addition, heat shock proteins are “molecular chaperones” that may protect directly or indirectly against apoptosis pathways. The role of enhanced endogenous heme oxygenase-1, heat shock protein overexpression, and heme oxygenase-1 downstream mediators, which protect against the ischemia/reperfusion injury, remain currently one of the most active areas of investigation. Summary Ischemia/reperfusion injury is a complex antigen-independent pathophysiologic process with a number of contributing factors that affect organ viability after transplantation. It is difficult to achieve effective protection by targeting individual mediators. Heme oxygenase-1 and heat shock proteins function to amplify multiple intracellular cytoprotective pathways against IRI, serve as a novel therapeutic concept in transplantation to maximize organ donor pool through the safer use of transplants despite prolonged periods of cold ischemia.