Lung transplantation is the only definitive ther-apy for end-stage pulmonary disease.Less than 20%of offered lungs are successfully transplanted due to a limited ischemic time window and poor donor lung quality man-ife...Lung transplantation is the only definitive ther-apy for end-stage pulmonary disease.Less than 20%of offered lungs are successfully transplanted due to a limited ischemic time window and poor donor lung quality man-ifested by pulmonary edema,hypoxia,or trauma.Therefore,poor donor organ recovery and utilization are significant barriers to wider implementation of the life-saving therapy of transplantation.While ischemia reperfusion injury(IRI)is often identified as the underlying molecular insult leading to immediate poor lung function in the post-operative period,this injury encompasses several pathways of cellular injury in addition to the recruitment of the innate immune system to the site of injury to propagate this inflammatory cascade.Pyroptosis is a central molecular inflammatory pathway that is the most significant contributor to injury in this early post-operative phase.Pyroptosis is another form of pro-grammed cell death and is often associated with IRI.The mitigation of pyroptosis in the early post-operative period following lung transplantation is a potential novel way to prevent poor allograft function and improve outcomes for all recipients.Here we detail the pyroptotic pathway,its importance in lung transplantation,and several therapeutic modalities that can mitigate this harmful inflammatory pathway.展开更多
基金supported through the National Institute of Health (NIH)grant R01 HL143000 and serves on the Clinical Events Committee of Trans Medics OCSsupported by the NIH grants:HL153876,EY030621,EY032583 and the American Heart Association grant:23TPA1142638supported through the Jewel and Frank Benson Family Endowment and The Jewel and Frank Benson Research Professorship at The Ohio State University.
文摘Lung transplantation is the only definitive ther-apy for end-stage pulmonary disease.Less than 20%of offered lungs are successfully transplanted due to a limited ischemic time window and poor donor lung quality man-ifested by pulmonary edema,hypoxia,or trauma.Therefore,poor donor organ recovery and utilization are significant barriers to wider implementation of the life-saving therapy of transplantation.While ischemia reperfusion injury(IRI)is often identified as the underlying molecular insult leading to immediate poor lung function in the post-operative period,this injury encompasses several pathways of cellular injury in addition to the recruitment of the innate immune system to the site of injury to propagate this inflammatory cascade.Pyroptosis is a central molecular inflammatory pathway that is the most significant contributor to injury in this early post-operative phase.Pyroptosis is another form of pro-grammed cell death and is often associated with IRI.The mitigation of pyroptosis in the early post-operative period following lung transplantation is a potential novel way to prevent poor allograft function and improve outcomes for all recipients.Here we detail the pyroptotic pathway,its importance in lung transplantation,and several therapeutic modalities that can mitigate this harmful inflammatory pathway.
