on August 12, 2004
Published online before print August 12, 2004, doi: 10.1161/01.ATV.0000141844.28073.df
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Submitted on May 19, 2004
Accepted on July 30, 2004
(1,3)Fucosyltransferases FucT-IV and FucT-VII Control Susceptibility to Atherosclerosis in Apolipoprotein E-/- Mice
Jonathon W. Homeister *;
From the Department of Pathology and The Howard Hughes Medical Institute (J.W.H., J.B.L.), University of Michigan, Ann Arbor, Mich; and the Department of Medicine (A.D.), Gill Heart Institute, University of Kentucky, Lexington.
* To whom correspondence should be addressed. E-mail: homeiste{at}umich.edu.
Objective--These studies examine the contributions of 
(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 (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.
Key words: atherosclerosis • apolipoprotein E • fucosyltransferase • monocyte • selectin
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