ATF3: A novel therapy thought in myocardial ischemia reperfusion injury other than in maladaptive cardiac remodeling

We have read an interesting paper titled “The cardiac maladaptive ATF3-dependent cross-talk between cardiomyocytes and macrophages is mediated by the IFNγ-CXCL10-CXCR3 axis” written by Koren and his colleagues [ [1] Koren L. Barash U. Zohar Y. et al. The cardiac maladaptive ATF3-dependent cross-talk between cardiomyocytes and macrophages is mediated by the IFNγ-CXCL10-CXCR3 axis. Int. J. Cardiol. 2016; 228: 394-400 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar ]. They investigated the roles of ATF3 against cardiac maladaptive remodeling and found that ATF3-KO mice escape from PE-dependent maladaptive cardiac remodeling by suppressing the IFNγ-CXCL10-CXCR3 axis at multiple levels. ATF3 belongs to the CREB family members, induced to transcriptional activation in several stressful conditions [ [2] Hai T.W. Liu F. Coukos W.J. Green M.R. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 1989; 3: 2083-2090 Crossref PubMed Scopus (755) Google Scholar ]. Recently, one research indicated that the inflammatory related cells were increasing in the ATF3-null hearts subjected to myocardial ischemic preconditioning and ischemia reperfusion [ [3] Brooks A.C. Guo Y. Singh M. et al. Endoplasmic reticulum stress-dependent activation of ATF3 mediates the late phase of ischemic preconditioning. J. Mol. Cell. Cardiol. 2014; 76: 138-147 Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar ]. Data from the above mentioned research suggested that ATF3 plays a cardio protective role in myocardial ischemia reperfusion injury [ [3] Brooks A.C. Guo Y. Singh M. et al. Endoplasmic reticulum stress-dependent activation of ATF3 mediates the late phase of ischemic preconditioning. J. Mol. Cell. Cardiol. 2014; 76: 138-147 Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar ]. Yet, the molecular mechanism is not currently known completely. Briefly, the cardioprotection of ATF3 is relation to suppression of inflammation and apoptosis by catalyzing histone deacetylation and leading the repression of transcriptional activation [ [2] Hai T.W. Liu F. Coukos W.J. Green M.R. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 1989; 3: 2083-2090 Crossref PubMed Scopus (755) Google Scholar ]. ATF3 inhibited inflammatory genes transcription by interfering the bindings of NF-κB [ [4] Whitmore M.M. Iparraguirre A. Kubelka L. et al. Negative regulation of TLR-signaling pathways by activating transcription factor-3. J. Immunol. 2007; 179: 3622-3630 Crossref PubMed Scopus (161) Google Scholar ]. Besides, Krivoruchko's study showed that ATF3 bonded to p53 promoter, inhibited p53 transcription and suppressed myocardial apoptosis, developing myocardium protective effect [ [5] Krivoruchko A. Storey K.B. Activation of the unfolded protein response during anoxia exposure in the turtle Trachemys scripta elegans. Mol. Cell. Biochem. 2013; 374: 91-103 Crossref PubMed Scopus (32) Google Scholar ].