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GATA2 Expression by Intima-Infiltrating Macrophages Drives Early Atheroma Formation

Charles Yin, Angela M. Vrieze, James Akingbasote, Emily N. Pawlak, Rajesh Abraham Jacob, Jonathan Hu, Neha Sharma, Jimmy D. Dikeakos, Lillian Barra, A. Dave Nagpal, View ORCID ProfileBryan Heit
doi: https://doi.org/10.1101/715565
Charles Yin
Department of Microbiology and Immunology, and the Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada
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Angela M. Vrieze
Department of Microbiology and Immunology, and the Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada
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James Akingbasote
Department of Microbiology and Immunology, and the Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada
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Emily N. Pawlak
Department of Microbiology and Immunology, and the Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada
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Rajesh Abraham Jacob
Department of Microbiology and Immunology, and the Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada
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Jonathan Hu
Department of Microbiology and Immunology, and the Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada
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Neha Sharma
Department of Microbiology and Immunology, and the Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada
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Jimmy D. Dikeakos
Department of Microbiology and Immunology, and the Center for Human Immunology, The University of Western Ontario, London, Ontario, Canada
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Lillian Barra
Department of Microbiology and Immunology, and the Center for Human Immunology, The University of Western Ontario, London, Ontario, CanadaDivision of Rheumatology, Department of Medicine, The University of Western Ontario, London, Ontario, Canada
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A. Dave Nagpal
Division of Cardiac Surgery, Department of Surgery, The University of Western Ontario, London, Ontario, CanadaDivision of Critical Care Medicine, Department of Medicine, The University of Western Ontario, London, Ontario, Canada
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Bryan Heit
Department of Microbiology and Immunology, and the Center for Human Immunology, The University of Western Ontario, London, Ontario, CanadaRobarts Research Institute, London, Ontario, Canada
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  • ORCID record for Bryan Heit
  • For correspondence: bheit@uwo.ca
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Abstract

Aberrant macrophage polarization is a major contributor to the onset and progression of atherosclerosis. Despite this, macrophage polarization during in early stages of human atherosclerotic disease is poorly understood. Using transcriptomic analysis of macrophages recovered from early-stage human atherosclerotic lesions, we have identified a unique gene expression profile dissimilar to that observed in later stages of disease that is characterized by upregulation of the hematopoietic transcription factor GATA2. GATA2 overexpression in vitro recapitulated defects observed in patient macrophages, including deficiencies in the uptake and processing of apoptotic cells, and in the catalysis of atherogenic protein modifications, with GATA2 knockdown abrogating these defects. Our data describe a previously unreported macrophage differentiation state present in early atheroma formation and identifies GATA2 as a driver of macrophage functional defects during the early stages of atherosclerosis in humans.

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Posted July 26, 2019.
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GATA2 Expression by Intima-Infiltrating Macrophages Drives Early Atheroma Formation
Charles Yin, Angela M. Vrieze, James Akingbasote, Emily N. Pawlak, Rajesh Abraham Jacob, Jonathan Hu, Neha Sharma, Jimmy D. Dikeakos, Lillian Barra, A. Dave Nagpal, Bryan Heit
bioRxiv 715565; doi: https://doi.org/10.1101/715565
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GATA2 Expression by Intima-Infiltrating Macrophages Drives Early Atheroma Formation
Charles Yin, Angela M. Vrieze, James Akingbasote, Emily N. Pawlak, Rajesh Abraham Jacob, Jonathan Hu, Neha Sharma, Jimmy D. Dikeakos, Lillian Barra, A. Dave Nagpal, Bryan Heit
bioRxiv 715565; doi: https://doi.org/10.1101/715565

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