期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 24, 期 10, 页码 1897-1903出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.ATV.0000141844.28073.df
关键词
atherosclerosis; apolipoprotein E; fucosyltransferase; monocyte; selectin
资金
- NCI NIH HHS [1P01CA71932] Funding Source: Medline
- NHLBI NIH HHS [HL06284] Funding Source: Medline
- NIGMS NIH HHS [GM62116] Funding Source: Medline
Objective - These studies examine the contributions of alpha(1,3) fucosyltransferases (FucT) IV and VII to the generation of selectin counter-receptors necessary for selectin-dependent atherogenesis. They also determine the functional contribution of FucT-IV and FucT-VII to shear-dependent tethering of monocytes to P-selectin, a process believed to be required for atherogenesis. Methods and Results - Atherosclerotic lesion size and histology were determined in apolipoprotein E-/- mice sufficient or deficient in FucT-IV or FucT-VII. Lesion size was subtly reduced in FucT-IV-deficient mice and significantly reduced in FucT-VII-deficient mice. FucT deficiency did not alter lesion histology, plasma total cholesterol, or the lipoprotein distribution profile. Atheroprotection in FucT-IV or FucT-VII deficiency aligned with subtle and profound reductions, respectively, of P-selectin counter-receptor activity on peripheral blood monocytes as determined by tethering to P-selectin-IgG in vitro under shear flow. Conclusions - FucT-VII-mediated alpha(1,3)fucosylation of selectin ligands is a necessary concomitant to atherogenesis in apoE-/- mice and is required for P-selectin-dependent peripheral blood monocyte adhesion under shear stress. FucT-IV deficiency yields subtle deficits in monocyte P-selectin counter-receptor activity and is associated with a subtle decrement in atherosclerosis. These studies identify an important role for FucT-VII in atherogenesis, and a subsidiary role for FucT-IV, and implicate leukocyte selectin counter-receptors in the pathogenesis of atherosclerosis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据