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Imaging mass spectrometry reveals heterogeneity of proliferation and metabolism
in atherosclerosis.
Authors Guillermier C, Doherty SP, Whitney AG, Babaev VR, Linton MF, Steinhauser ML,
Brown JD
Submitted By Submitted Externally on 8/6/2019
Status Published
Journal JCI insight
Year 2019
Date Published 6/1/2019
Volume : Pages 4 : Not Specified
PubMed Reference 31167964
Abstract Atherosclerotic plaques feature local proliferation of leukocytes and vascular
smooth muscle cells (VSMCs) and changes in cellular metabolism. Yet the
relationship between glucose utilization and proliferation has been technically
impossible to study directly in cells of atherosclerotic plaques in vivo. We
used multi-isotope imaging mass spectrometry (MIMS), a quantitative imaging
platform, to measure coincident cell division and glucose utilization at
suborganelle resolution in atherosclerotic plaques. In established plaques, 65%
of intimal foam cells and only 4% of medial VSMCs were labeled with
15N-thymidine after 1 week of isotope treatment. Dividing cells demonstrated
heightened glucose labeling. MIMS detected 2H-glucose label in multiple
subcellular compartments within foam cells, including lipid droplets, the
cytosol, and chromatin. Unexpectedly, we identified an intensely focal region of
2H-label in VSMCs underlying plaques. This signal diminished in regions of aorta
without atherosclerosis. In advanced plaques, 15N-thymidine and 2H-glucose
labeling in foam cells and VSMCs significantly decreased. These data demonstrate
marked heterogeneity in VSMC glucose metabolism that was dependent on both
proliferative status and proximity of VSMCs to plaques. Furthermore, these
results reveal how quantitative mass spectrometry coupled with isotope imaging
can complement other methods used to study cell biology directly in the growing
atherosclerotic plaque in vivo.


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