Functional Role of CD11c+ Monocytes in Atherogenesis Associated With Hypercholesterolemia

被引：207

作者：

Wu, Huaizhu ^{[1
,2
,5
,6
]}

Gower, R. Michael ^{[7
]}

Wang, Hong ^{[2
,8
]}

Perrard, Xiao-Yuan Dai ^{[2
,6
]}

Ma, Ruidong ^{[3
]}

Bullard, Daniel C. ^{[9
]}

Burns, Alan R. ^{[1
,5
]}

Paul, Antoni ^{[4
]}

Smith, C. Wayne ^{[1
,5
]}

Simon, Scott I. ^{[7
]}

Ballantyne, Christie M. ^{[1
,2
,5
,6
]}

机构：

[1] Baylor Coll Med, Dept Med, Houston, TX 77030 USA

[2] Baylor Coll Med, Sect Atherosclerosis & Vasc Med, Houston, TX 77030 USA

[3] Baylor Coll Med, Thrombosis Res Sect, Houston, TX 77030 USA

[4] Baylor Coll Med, Div Endocrinol Diabet & Metab, Houston, TX 77030 USA

[5] Baylor Coll Med, Sect Leukocyte Biol, Houston, TX 77030 USA

[6] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA

[7] Univ Calif Davis, Dept Bioengn, Davis, CA USA

[8] Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19122 USA

[9] Univ Alabama, Dept Genet, Div Res, Birmingham, AL USA

来源：

CIRCULATION | 2009年 / 119卷 / 20期

基金：

美国国家卫生研究院;

关键词：

atherosclerosis; cell adhesion molecules; leukocytes; FOAM CELL-FORMATION; INFLAMMATORY RESPONSE; LY-6C(HI) MONOCYTES; ATHEROSCLEROSIS; MICE; ACCUMULATION; DEFICIENCY; CD11C/CD18; PATHOGENESIS; MACROPHAGES;

D O I：

10.1161/CIRCULATIONAHA.108.823740

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background-Monocyte activation and migration into the arterial wall are key events in atherogenesis associated with hypercholesterolemia. CD11c/CD18, a beta(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. (Circulation. 2009; 119: 2708-2717.)

引用

页码：2708 / U113

页数：22

共 30 条

[1] P-selectin glycoprotein ligand-1 is highly expressed on Ly-6Chi monocytes and a major determinant for Ly-6Chi monocyte recruitment to sites of atherosclerosis in mice [J].