The Hsp70.3 isoform of Hsp70, but not Hsp70.1, contributes to NF‐kappaB‐dependent cardioprotection of late ischemic preconditioning

Abstract

It has been shown by our lab and others that the transcription factor NF‐κB is necessary for the development of the late window of protection after ischemic preconditioning (IPC) in the heart. However, the specific mechanisms and downstream gene expression profiles that underlie the cardioprotection of NF‐κB in late IPC remain unknown. To investigate NF‐κB‐dependent gene expression in IPC, we conducted a directed microarray analysis to compare the gene expression patterns of wild‐type and NF‐κB dominant negative mice 3.5 hrs after an IPC stimulus. Among the potential cardioprotective candidates identified by gene array analysis as being regulated in an NF‐κB‐dependent manner after IPC were both isoforms of heat shock protein 70 (Hsp70.1 and Hsp70.3). An in vivo mouse model of IPC followed 24 hours later by a 30 minute ischemia and reperfusion was used to assess the impact of Hsp70 isoform expression on late IPC induced cardioprotection. As previously shown by others, an Hsp70.1/70.3 double knockout mouse model failed to exhibit a cardioprotective phenotype during the late window of IPC. However, the Hsp70.1 single isoform knockout exhibited late IPC cardioprotection similar to that of wild‐type mice. In conclusion, this work demonstrates that while both Hsp70.1 and Hsp70.3 expression are induced by NF‐κB after an IPC stimulus, only the Hsp70.3 isoform contributes to cardioprotection in the late phase of IPC. This work was supported by NIH grant R01 HL63034 (WKJ) and NSF award number 0333377.