deletion of the innate immune nlrp3 receptor abolishes cardiac ischemic preconditioning and is associated with decreased il-6stat3 signaling删除的先天免疫nlrp3受体破坏心脏缺血预处理和与il-6stat3信号下降有关.pdfVIP

Deletion of the Innate Immune NLRP3 Receptor Abolishes Cardiac Ischemic Preconditioning and Is Associated with Decreased Il-6/STAT3 Signaling 1 . 1. 2 1 3 Coert J. Zuurbier * , Willeke M. C. Jong , Otto Eerbeek , Anneke Koeman , Wilco P. Pulskens , 3 3 1 Loes M. Butter , Jaklien C. Leemans , Markus W. Hollmann 1 Laboratory of Experimental Intensive Care and Anesthesiology, Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 2 Department of Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 3 Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Abstract Objective: Recent studies indicate that the innate immune system is not only triggered by exogenous pathogens and pollutants, but also by endogenous danger signals released during ischemia and necrosis. As triggers for the innate immune NLRP3 inflammasome protein complex appear to overlap with those for cardiac ischemia-reperfusion (I/R) and ischemic preconditioning (IPC), we explored the possibility that the NLRP3 inflammasome is involved in IPC and acute I/R injury of the heart. Principal Findings: Baseline cardiac performance and acute I/R injury were investigated in isolated, Langendorff-perfused hearts from wild-type (WT), ASC2/ 2 and NLRP32/ 2 mice. Deletion of NLRP3 inflammasome components ASC2/ 2 or NLRP32/ 2 did not affect baseline performance. The deletions exacerbated I/R-induced mechanical dysfunction, but were without effect on I/R-induced cell death. When subjected to IPC, WT and ASC2/ 2 heart