RT Journal Article
SR Electronic
T1 GATA2 Expression by Intima-Infiltrating Macrophages Drives Early Atheroma Formation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 715565
DO 10.1101/715565
A1 Charles Yin
A1 Angela M. Vrieze
A1 James Akingbasote
A1 Emily N. Pawlak
A1 Rajesh Abraham Jacob
A1 Jonathan Hu
A1 Neha Sharma
A1 Jimmy D. Dikeakos
A1 Lillian Barra
A1 A. Dave Nagpal
A1 Bryan Heit
YR 2019
UL http://biorxiv.org/content/early/2019/07/26/715565.abstract
AB 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.