Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia

Academic Article

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. © 2009 American Heart Association, Inc.
  • Authors

    Published In

  • Circulation  Journal
  • Digital Object Identifier (doi)

    Author List

  • Wu H; Gower RM; Wang H; Perrard XYD; Ma R; Bullard DC; Burns AR; Paul A; Smith CW; Simon SI
  • Start Page

  • 2708
  • End Page

  • 2717
  • Volume

  • 119
  • Issue

  • 20