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NF‐κB ORCHESTRATES GENE EXPRESSION ASSOCIATED WITH MYOCARDIAL INFARCTION AND PROTECTION
Author(s) -
Wilhide Michael E.,
Tranter Michael,
Ren Xiaoping,
Jones W. Keith
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1133.2
Subject(s) - cardioprotection , nf κb , heat shock protein , hsp70 , microbiology and biotechnology , endoplasmic reticulum , apoptosis , gene , biology , gene expression , myocardial infarction , medicine , signal transduction , genetics
NF‐κB has been shown to contribute to myocardial infarction (MI) after ischemia/reperfusion (I/R) and to cardioprotection after permanent coronary occlusion (PO). The aim is to discover the mechanism by which NF‐κB regulates these opposing effects after MI. The hypothesis is that, after different ischemic stimuli, NF‐κB mediates different sets of genes that are responsible for opposite effects. We employed transgenic mice that block NF‐κB in a cardiac‐specific manner. These mice were subjected either to I/R or PO and microarrays were used to delineate the genes regulated acutely by NF‐κB. Interestingly, after I/R NF‐κB activation leads to at least a two‐fold increase in the expression levels of several heat shock proteins. After PO, NF‐κB leads to a three‐fold higher level of Hsp70 compared to I/R. Cox2 was also found to be differentially expressed. Different heat shock proteins are known to be either anti‐apoptotic or pro‐apoptotic, and HSPs may affect processing and activity of Cox2 via endoplasmic reticulum (ER) stress response/processing pathways. Thus, HSP and Cox2 regulation by NF‐κB may underlie, at least in part, the differential effects of NF‐κB. Understanding the role of NF‐κB in the regulation of these sets of genes will aid in the discovery of novel therapeutic targets for the treatment of heart disease. This work was supported by NIH grant R01 HL63034 (WKJ) and 5F31 HL081923 (MW).