Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis

Nagareddy, P. R., Murphy, A. J., Stirzaker, R. A., Hu, Y., Yu, S., Miller, R. G., Ramkhelawon, B., Distel, E., Westerterp, M., Huang, L-S., Schmidt, A. M., Orchard, T. J., Fisher, E. A., Tall, A. R. & Goldberg, I. J., 2013, In : Cell metabolism. 17, 5, p. 695-708 14 p.

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  • Hyperglycemia Promotes Myelopoiesis and Impairs the Resolution of Atherosclerosis

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  • Prabhakara R Nagareddy
  • Andrew J Murphy
  • Roslynn A Stirzaker
  • Yunying Hu
  • Shiquing Yu
  • Rachel G Miller
  • Bhama Ramkhelawon
  • Emilie Distel
  • Marit Westerterp
  • Li-Shin Huang
  • Ann Marie Schmidt
  • Trevor J Orchard
  • Edward A Fisher
  • Alan R Tall
  • Ira J Goldberg

Diabetes is a major risk factor for atherosclerosis. Although atherosclerosis is initiated by deposition of cholesterol-rich lipoproteins in the artery wall, the entry of inflammatory leukocytes into lesions fuels disease progression and impairs resolution. We show that diabetic mice have increased numbers of circulating neutrophils and Ly6-C(hi) monocytes, reflecting hyperglycemia-induced proliferation and expansion of bone marrow myeloid progenitors and release of monocytes into the circulation. Increased neutrophil production of S100A8/S100A9, and its subsequent interaction with the receptor for advanced glycation end products on common myeloid progenitor cells, leads to enhanced myelopoiesis. Treatment of hyperglycemia reduces monocytosis, entry of monocytes into atherosclerotic lesions, and promotes regression. In patients with type 1 diabetes, plasma S100A8/S100A9 levels correlate with leukocyte counts and coronary artery disease. Thus, hyperglycemia drives myelopoiesis and promotes atherogenesis in diabetes.

Original languageEnglish
Pages (from-to)695-708
Number of pages14
JournalCell metabolism
Issue number5
Publication statusPublished - 2013


  • Animals, Atherosclerosis/metabolism, Bone Marrow/metabolism, Coronary Disease/metabolism, Cytokines/metabolism, Diabetes Mellitus, Experimental/metabolism, Diabetes Mellitus, Type 1/metabolism, Glucose/metabolism, Glycation End Products, Advanced/metabolism, Humans, Hyperglycemia/metabolism, Leukocytes/metabolism, Leukocytosis/metabolism, Male, Mice, Mice, Inbred C57BL, Monocytes/metabolism, Myeloid Progenitor Cells/metabolism, Myelopoiesis/physiology, NF-kappa B/metabolism, Neutrophils/metabolism, Receptor for Advanced Glycation End Products, Receptors, Immunologic/metabolism

ID: 76396811