Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia

Circulation. 2009 May 26;119(20):2708-17. doi: 10.1161/CIRCULATIONAHA.108.823740. Epub 2009 May 11.


Background: Monocyte activation and migration into the arterial wall are key events in atherogenesis associated with hypercholesterolemia. CD11c/CD18, a beta2 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Atherosclerosis / etiology*
  • CD11c Antigen / analysis
  • CD11c Antigen / genetics
  • CD11c Antigen / physiology*
  • Chemotaxis, Leukocyte
  • E-Selectin / metabolism
  • Hypercholesterolemia / complications*
  • Mice
  • Mice, Knockout
  • Monocytes / pathology
  • Monocytes / physiology*
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Apolipoproteins E
  • CD11c Antigen
  • E-Selectin
  • Vascular Cell Adhesion Molecule-1