Reduced plaque formation induced by rosiglitazone in an STZ-diabetes mouse model of atherosclerosis is associated with downregulation of adhesion molecules

被引：31

作者：

Tikellis, C. ^{[1
]}

Jandeleit-Dahm, K. A. ^{[1
]}

Sheehy, K. ^{[1
]}

Murphy, A. ^{[1
]}

Chin-Dusting, J. ^{[1
]}

Kling, D. ^{[2
]}

Sebokova, E. ^{[2
]}

Cooper, M. E. ^{[1
]}

Mizrahi, J. ^{[2
]}

Woollard, K. J. ^{[1
]}

机构：

[1] Baker Med Res Inst, Melbourne, Vic 8008, Australia

[2] F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland

来源：

ATHEROSCLEROSIS | 2008年 / 199卷 / 01期

关键词：

P-selectin; adhesion molecules; atherosclerosis; rosiglitazone; plaque;

D O I：

10.1016/j.atherosclerosis.2007.10.038

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Adhesion molecules have been implicated in the development and progression of cardiovascular disease, which is highly prevalent in people with diabetes. Adhesion molecules can mediate adhesion of leukocytes to the endothelium. Furthermore, P-selectin expressed on platelets is able to mediate the adhesion of leukocytes to platelets. In this study, we examine the in-vivo and in-vitro effects of rosiglitazone with particular emphasis on three important adhesion molecules (VCAM-1, ICAM-1 and P-selectin). In the aorta of STZ-diabetic apolipoprotein E-deficient (apoE KO) mice, rosiglitazone significantly reduced both total and arch plaque area. The mechanism for this appeared to be reduced macrophage infiltration into the atherosclerotic plaque which was also associated with reduced mRNA levels for VCAM-1, ICAM-1, MCP-1 and P-selectin in the aorta. In-vitro studies revealed reduced cell adhesion of monocytic cells (THP-1) to fibrinogen and endothelial cells (HUVEC) after incubation with rosiglitazone. Furthermore, the reduction in leukocyte adhesion also correlated with significant reductions in mRNA levels for VCAM-1, ICAM-1 and P-selectin indicating that reduced macrophage infiltration in atherosclerotic plaques may occur as a result of a direct effect of rosiglitazone on adhesion molecules in both monocytes and endothelial cells. Thus, we have shown that rosiglitazone appears to have direct anti-atherosclerotic effects in an animal model of diabetes-associated atherosclerosis which are at least partly due to effects on VCAM-1, ICAM-1, MCP-1 and P-selectin expression which leads to decreased leukocyte adhesion and macrophage infiltration. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

引用

页码：55 / 64

页数：10

共 48 条

[1] Respiratory syncytial virus infection of human lung endothelial cells enhances selectively intercellular adhesion molecule-1 expression [J].