| Literature DB >> 23663738 |
Prabhakara R Nagareddy1, 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.
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.Entities:
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Year: 2013 PMID： 23663738 PMCID： PMC3992275 DOI： 10.1016/j.cmet.2013.04.001
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287