Hyperglycemia Promotes Myelopoiesis and Impairs the Resolution of Atherosclerosis

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• 作者：Prabhakara R. Nagareddy¹ ; ⁵ ; Andrew J. Murphy² ; ⁵ ; Roslynn A. Stirzaker¹ ; Yunying Hu¹ ; Shiquing Yu¹ ; Rachel G. Miller³ ; Bhama Ramkhelawon⁴ ; Emilie Distel⁴ ; Marit Westerterp² ; Li-Shin Huang¹ ; Ann Marie Schmidt⁴ ; Trevor J. Orchard³ ; Edward A. Fisher⁴ ; Alan R. Tall² ; ⁶ ; Ira J. Goldberg¹ ; ⁶ ; ^{ijg3@columbia.edu}
• 刊名：Cell Metabolism
• 出版年：2013
• 出版时间：7 May, 2013
• 年：2013
• 卷：17
• 期：5
• 页码：695-708
• 全文大小：2365 K

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Summary

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.