Functional Role of CD11c + Monocytes in Atherogenesis Associated With Hypercholesterolemia

• DOI: 10.1161/circulationaha.108.823740
• Publication Date: 2009-05-12T01:29:03Z
• Authors: Huaizhu Wu; R. Michael Gower; Hong Wang; Xiao-Yuan Dai Per...; Ruidong Ma; Daniel C. Bullard; Alan R. Burns; Antoni Paul; C. Wayne Smith; Scott I. Simon; Christie M. Balla...
• Keywords: Mice, Knockout; 0303 health sciences; leukocytes; Hypercholesterolemia; 610; Vascular Cell Adhesion Molecule-1; Chemical Engineering; Atherosclerosis; Monocytes; CD11c Antigen; cell adhesion molecules; Chemotaxis, Leukocyte; Mice; 03 medical and health sciences; Apolipoproteins E; 616; Animals; atherosclerosis; E-Selectin; Biomedical Engineering and Bioengineering

Background—

Monocyte activation and migration into the arterial wall are key events in atherogenesis associated with hypercholesterolemia. CD11c/CD18, a β 2 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.