Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia

Huaizhu Wu, R. Michael Gower, Hong Wang, Xiao Yuan Dai Perrard, Ruidong Ma, Daniel C. Bullard, Alan R. Burns, Antoni Paul, C. Wayne Smith, Scott I. Simon, Christie M. Ballantyne

Research output: Contribution to journalArticle

147 Scopus citations

Abstract

BACKGROUND-: Monocyte activation and migration into the arterial wall are key events in atherogenesis associated with hypercholesterolemia. CD11c/CD18, a β2 integrin expressed on human monocytes and a subset of mouse monocytes, has been shown to play a distinct role in human monocyte adhesion on endothelial cells, but the regulation of CD11c in hypercholesterolemia and its role in atherogenesis are unknown. METHODS AND RESULTS-: Mice genetically deficient in CD11c were generated and crossbred with apolipoprotein E (apoE) mice to generate CD11c/apoE mice. Using flow cytometry, we examined CD11c on blood leukocytes in apoE hypercholesterolemic mice and found that compared with wild-type and apoE mice on a normal diet, apoE mice on a Western high-fat diet had increased CD11c monocytes. Circulating CD11c monocytes from apoE mice fed a high-fat diet exhibited cytoplasmic lipid vacuoles and expressed higher levels of CD11b and CD29. Deficiency of CD11c decreased firm arrest of mouse monocytes on vascular cell adhesion molecule-1 and E-selectin in a shear flow assay, reduced monocyte/macrophage accumulation in atherosclerotic lesions, and decreased atherosclerosis development in apoE mice on a high-fat diet. CONCLUSIONS-: CD11c, which increases on blood monocytes during hypercholesterolemia, plays an important role in monocyte recruitment and atherosclerosis development in an apoE mouse model of hypercholesterolemia.

Original languageEnglish (US)
Pages (from-to)2708-2717
Number of pages10
JournalCirculation
Volume119
Issue number20
DOIs
StatePublished - May 26 2009

Keywords

  • Atherosclerosis
  • Cell adhesion molecules
  • Leukocytes

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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    Wu, H., Gower, R. M., Wang, H., Perrard, X. Y. D., Ma, R., Bullard, D. C., Burns, A. R., Paul, A., Smith, C. W., Simon, S. I., & Ballantyne, C. M. (2009). Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia. Circulation, 119(20), 2708-2717. https://doi.org/10.1161/CIRCULATIONAHA.108.823740