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Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis

Prabhakara R Nagareddy1, Andrew J Murphy, Roslynn A Stirzaker

  • 1Division of Preventive Medicine and Nutrition, Department of Medicine, Columbia University, New York, NY 10032, USA.

Cell Metabolism
|May 14, 2013
PubMed

Insights

Hyperglycemia in diabetes promotes atherosclerosis by increasing white blood cell production and infiltration into artery walls. Managing blood sugar levels can reduce these effects and promote lesion regression.

Area of Science:

  • Cardiovascular Science
  • Immunology
  • Endocrinology

Background:

  • Diabetes mellitus is a significant risk factor for atherosclerosis.
  • Atherosclerosis progression is exacerbated by inflammatory leukocyte infiltration into arterial lesions.
  • Hyperglycemia is implicated in altered immune cell dynamics during diabetes.

Purpose of the Study:

  • To investigate the mechanisms by which hyperglycemia drives myelopoiesis and promotes atherogenesis in diabetes.
  • To determine the role of S100A8/S100A9 in hyperglycemia-induced immune cell expansion.
  • To assess the impact of hyperglycemia treatment on monocytosis and atherosclerotic lesion development.

Main Methods:

  • Induction of diabetes and atherosclerosis in mouse models.
  • Analysis of bone marrow myeloid progenitor proliferation and monocyte counts.
  • Measurement of S100A8/S100A9 levels and their interaction with the receptor for advanced glycation end products.
  • Assessment of leukocyte infiltration into atherosclerotic lesions and lesion regression following hyperglycemia treatment.
  • Correlation analysis of plasma S100A8/S100A9 with leukocyte counts and coronary artery disease in type 1 diabetes patients.

Main Results:

  • Diabetic mice exhibit increased circulating neutrophils and Ly6-C(hi) monocytes due to hyperglycemia-driven bone marrow myeloid progenitor expansion.
  • Neutrophil-derived S100A8/S100A9 enhances myelopoiesis by interacting with the receptor for advanced glycation end products on myeloid progenitors.
  • Hyperglycemia treatment effectively reduces monocytosis, leukocyte infiltration into atherosclerotic lesions, and promotes lesion regression.
  • Elevated plasma S100A8/S100A9 levels in type 1 diabetes patients correlate with leukocyte counts and coronary artery disease.

Conclusions:

  • Hyperglycemia is a key driver of increased myelopoiesis and subsequent atherogenesis in diabetes.
  • The S100A8/S100A9 pathway plays a critical role in mediating hyperglycemia-induced immune cell expansion.
  • Targeting hyperglycemia and associated inflammatory pathways offers a potential therapeutic strategy for diabetic cardiovascular complications.

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