Published Online
on May 11, 2009

A more recent version of this article appeared on May 26, 2009

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Submitted on September 24, 2008
Accepted on April 2, 2009

Functional Role of CD11c⁺ Monocytes in Atherogenesis Associated With Hypercholesterolemia

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

From the Section of Atherosclerosis and Vascular Medicine (H. Wu, H.Wang, X.D.P., C.M.B.), Section of Thrombosis Research (R.M.), Division of Diabetes, Endocrinology, and Metabolism (A.P.), Department of Medicine, and Section of Leukocyte Biology, Department of Pediatrics (H. Wu, A.R.B., C.W.S., C.M.B.), Baylor College of Medicine, Houston, Tex; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, Tex (H. Wu, X.D.P., C.M.B.); Department of Bioengineering, University of California at Davis (R.M.G., S.I.S.); Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pa (H. Wang); and Department of Genetics, Research Division, University of Alabama at Birmingham (D.C.B.). Dr Burns is currently affiliated with the College of Optometry, University of Houston, Houston, Tex.

^* To whom correspondence should be addressed. E-mail: cmb{at}bcm.tmc.edu.

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

Key words: atherosclerosis • cell adhesion molecules • leukocytes

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Clinical Summaries
Circulation 2009 119: 2645-2646. [Extract] [Full Text]

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