RGD Reference Report - Identification of a NF-kappaB cardioprotective gene program: NF-kappaB regulation of Hsp70.1 contributes to cardioprotection after permanent coronary occlusion. - Rat Genome Database

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Identification of a NF-kappaB cardioprotective gene program: NF-kappaB regulation of Hsp70.1 contributes to cardioprotection after permanent coronary occlusion.

Authors: Wilhide, ME  Tranter, M  Ren, X  Chen, J  Sartor, MA  Medvedovic, M  Jones, WK 
Citation: Wilhide ME, etal., J Mol Cell Cardiol. 2011 Jul;51(1):82-9. doi: 10.1016/j.yjmcc.2011.03.011. Epub 2011 Mar 23.
RGD ID: 7257651
Pubmed: PMID:21439970   (View Abstract at PubMed)
PMCID: PMC3569977   (View Article at PubMed Central)
DOI: DOI:10.1016/j.yjmcc.2011.03.011   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Coronary Occlusion  IEP 7257651mRNA:increased expression:heart:RGD 
Coronary Occlusion  ISOHSPA1A (Homo sapiens)7257651; 7257651mRNA:increased expression:heart:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hspa1a  (heat shock protein family A (Hsp70) member 1A)

Genes (Mus musculus)
Hspa1a  (heat shock protein 1A)

Genes (Homo sapiens)
HSPA1A  (heat shock protein family A (Hsp70) member 1A)


Additional Information