Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis

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

doi:10.1016/j.cmet.2013.04.001

Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis

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

Research output: Contribution to journal › Article › peer-review

459 Scopus citations

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.

Original language	English
Pages (from-to)	695-708
Number of pages	14
Journal	Cell Metabolism
Volume	17
Issue number	5
DOIs	https://doi.org/10.1016/j.cmet.2013.04.001
State	Published - 7 May 2013
Externally published	Yes

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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). Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metabolism, 17(5), 695-708. https://doi.org/10.1016/j.cmet.2013.04.001

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title = "Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis",

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-Chi 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.",

author = "Nagareddy, {Prabhakara R.} and Murphy, {Andrew J.} and Stirzaker, {Roslynn A.} and Yunying Hu and Shiquing Yu and Miller, {Rachel G.} and Bhama Ramkhelawon and Emilie Distel and Marit Westerterp and Huang, {Li Shin} and Schmidt, {Ann Marie} and Orchard, {Trevor J.} and Fisher, {Edward A.} and Tall, {Alan R.} and Goldberg, {Ira J.}",

note = "Funding Information: We thank ISIS Pharmaceuticals and Bristol-Myers Squibb for providing SGLT2 inhibitors. We also acknowledge the assistance from the Flow Cytometry and Imaging Core Facilities at Columbia University. This project was funded by NIH grants U01-HL087945 and DK095684 (Dual-PI grants to I.J.G. and E.A.F.), P01-HL54591 and a Pilot and feasibility Award from the Diabetes Complications Consortium (to I.J.G.), and HL87123 and HL107653 (to A.R.T.). P.R.N. was supported by a postdoctoral fellowship from the Canadian Institutes of Health Research, and A.J.M. was supported by a postdoctoral fellowship from the American Heart Association (12POST11890019). ",

year = "2013",

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doi = "10.1016/j.cmet.2013.04.001",

language = "English",

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T1 - Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis

AU - Nagareddy, Prabhakara R.

AU - Murphy, Andrew J.

AU - Stirzaker, Roslynn A.

AU - Hu, Yunying

AU - Yu, Shiquing

AU - Miller, Rachel G.

AU - Ramkhelawon, Bhama

AU - Distel, Emilie

AU - Westerterp, Marit

AU - Huang, Li Shin

AU - Schmidt, Ann Marie

AU - Orchard, Trevor J.

AU - Fisher, Edward A.

AU - Tall, Alan R.

AU - Goldberg, Ira J.

N1 - Funding Information: We thank ISIS Pharmaceuticals and Bristol-Myers Squibb for providing SGLT2 inhibitors. We also acknowledge the assistance from the Flow Cytometry and Imaging Core Facilities at Columbia University. This project was funded by NIH grants U01-HL087945 and DK095684 (Dual-PI grants to I.J.G. and E.A.F.), P01-HL54591 and a Pilot and feasibility Award from the Diabetes Complications Consortium (to I.J.G.), and HL87123 and HL107653 (to A.R.T.). P.R.N. was supported by a postdoctoral fellowship from the Canadian Institutes of Health Research, and A.J.M. was supported by a postdoctoral fellowship from the American Heart Association (12POST11890019).

PY - 2013/5/7

Y1 - 2013/5/7

N2 - 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-Chi 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.

AB - 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-Chi 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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DO - 10.1016/j.cmet.2013.04.001

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SN - 1550-4131

VL - 17

SP - 695

EP - 708

JO - Cell Metabolism

JF - Cell Metabolism

IS - 5

ER -

Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis

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