| Authors |
Nagareddy PR, Murphy AJ, Stirzaker RA, Hu Y, Yu S, Miller RG, Ramkhelawon B,
Distel E, Westerterp M, Huang LS, Schmidt AM, Orchard TJ, Fisher EA, Tall AR,
Goldberg IJ
|
| Submitted By |
Ira Goldberg on 2/19/2014 |
| Status |
Published |
| Journal |
Cell Metabolism |
| Year |
2013 |
| Date Published |
5/7/2013 |
| Volume : Pages |
17 : 695 - 708 |
| PubMed Reference |
23663738 |
| Abstract |
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.
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