Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia.
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.


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.
Section of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Huaizhu
H
Wu
R Michael
RM
Gower
Hong
H
Wang
Xiao-Yuan Dai
XY
Perrard
Ruidong
R
Ma
Daniel C
DC
Bullard
Alan R
AR
Burns
Antoni
A
Paul
C Wayne
CW
Smith
Scott I
SI
Simon
Christie M
CM
Ballantyne
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000209:etiology*; D039521:CD11c Antigen / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D019040:E-Selectin / Q000378:metabolism; D006937:Hypercholesterolemia / Q000150:complications*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000473:pathology / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D001057:Apolipoproteins E; D039521:CD11c Antigen; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1