| First Author | Wilhide ME | Year | 2011 |
| Journal | J Mol Cell Cardiol | Volume | 51 |
| Issue | 1 | Pages | 82-9 |
| PubMed ID | 21439970 | Mgi Jnum | J:173789 |
| Mgi Id | MGI:5050363 | Doi | 10.1016/j.yjmcc.2011.03.011 |
| Citation | Wilhide ME, et al. (2011) Identification of a NF-kappaB cardioprotective gene program: NF-kappaB regulation of Hsp70.1 contributes to cardioprotection after permanent coronary occlusion. J Mol Cell Cardiol 51(1):82-9 |
| abstractText | The transcription factor Nuclear Factor Kappa B (NF-kappaB) has been shown to be cardioprotective after permanent coronary occlusion (PO) and late ischemic preconditioning (IPC), and yet it is cell injurious after ischemia/reperfusion (I/R) in the heart. There is limited information regarding NF-kappaB-dependent cardioprotection, and the NF-kappaB-dependent genes that contribute to the cardioprotection after PO are completely unknown. The objective of the study was to identify NF-kappaB-dependent genes that contribute to cardioprotection after PO. Microarray analysis was used to delineate genes that potentially contribute to the NF-kappaB-dependent cardioprotection by determining the overlap between the set of PO regulated genes and genes regulated by NF-kappaB, using mice with genetic abrogation of NF-kappaB activation in the heart. This analysis identified 16 genes as candidates for NF-kappaB-dependent effects after PO. This set of genes overlaps with, but is significantly different from the set of genes we previously identified as regulated by NF-kappaB after IPC. The genes encoding heat shock protein 70.3 (hspa1a) and heat shock protein 70.1 (hspa1b) were the most significantly regulated genes after PO and were up-regulated by NF-kappaB. Results using knockout mice show that Hsp70.1 contributes to NF-kappaB-dependent cardioprotection after PO and likely underlies, at least in part, the NF-kappaBeta-dependent cardioprotective effect. Our previous results show that Hsp70.1 is injurious after I/R injury. This demonstrates that, like NF-kappaB itself, Hsp70.1 has antithetical effects on myocardial survival and suggests that this may underlie the similar antithetical effects of NF-kappaB after different ischemic stimuli. The significance of the research is that understanding the gene network regulated by NF-kappaB after ischemic insult may lead to identification of therapeutic targets more appropriate for clinical development. |
