Inflammatory chemokine transport and presentation in HEV. associated with the presence of a Indigo large number of proinflammatory Ly6Chi monocytes/macrophages and fewer reparative Ly6Clo macrophages in the myocardium of mGATA3KO mice compared with control mice. Analysis of serum proteins from the 2 2 mouse genotypes revealed no major changes in the profile of serum growth factors and cytokines between the 2 mice genotypes before and after MI. GATA3 was found to be specifically and transiently induced by interleukin 4 in cultured macrophages through activity of the proximal promoter, whereas the distal promoter remained silent. In addition, the absence of GATA3 in macrophages markedly attenuated arginase-1 expression in cultured macrophages. CONCLUSIONS: We demonstrated that the presence of GATA3-positive macrophages adversely affects remodeling of the myocardium in response to ischemia or pressure overload, whereas the absence of these macrophages led to a significant improvement in cardiac function. Targeting of signaling pathways that lead to the expression of GATA3 in macrophages may have favorable cardiac outcomes. Inflammation modulates LV remodeling in murine models of coronary occlusion or pressure overload. In this study, myocardial infiltration of monocytes-macrophages deficient in GATA3 was associated with less adverse LV remodeling and better preservation of LVEF, demonstrating the complex role of macrophage phenotypes in LV remodeling. Further studies are needed to define the role of myeloid expression of GATA3 in LV remodeling in human subjects after acute MI or LV pressure load. If confirmed, modulating macrophage expression of Indigo GATA3 may provide a novel therapeutic target to attenuate adverse LV remodeling. Disclosures: The Indigo authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher’s Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. REFERENCES 1. Murray PJ, Wynn TA. Protective and pathogenic Indigo functions of macrophage subsets. Nat Rev Immunol 2011;11:723C37. [PMC free article] [PubMed] [Google Scholar] 2. McNelis Indigo Joanne C, Olefsky Jerrold M. Macrophages, immunity, and metabolic disease. Immunity 2014;41:36C48. [PubMed] [Google Scholar] 3. Schulz C, Perdiguero EG, Chorro L, et al. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 2012;336:86C90. [PubMed] [Google Scholar] 4. Yona S, Kim K-W, Wolf Y, et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 2013;38:79C91. [PMC free article] [PubMed] [Google Scholar] 5. Hashimoto D, Chow A, Noizat C, et al. Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 2013;38:792C804. [PMC free article] [PubMed] [Google Scholar] 6. Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. Development of monocytes, macrophages, and dendritic cells. Science 2010;327:656C61. [PMC free article] [PubMed] [Google Scholar] 7. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008;8:958C69. [PMC free article] [PubMed] [Google Scholar] 8. Lawrence T, Natoli G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol 2011;11:750C61. [PubMed] [Google Scholar] 9. Xue J, Schmidt SV, Sander J, et al. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity 2014;40:274C88. [PMC free ARMD5 article] [PubMed] [Google Scholar] 10. Glass CK, Natoli G. Molecular control of activation and priming in macrophages. Nat Immunol 2016;17:26C33. [PMC free article] [PubMed] [Google Scholar] 11. Zhu J Transcriptional regulation of Th2 cell differentiation. Immunol Cell Biol 2010;88:244C9. [PMC free article] [PubMed] [Google Scholar] 12. Ting CN, Olson MC, Barton KP, Leiden JM. Transcription factor GATA-3 is required for development of the T-cell lineage. Nature 1996;384:474C8. [PubMed].
