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Core2 1-6-N-glucosaminyltransferase-I is Crucial for the Formation of Atherosclerotic Lesions in Apolipoprotein E-deficient Mice

Overview

Overview

Journal Arterioscler Thromb Vasc Biol

Date 2008 Dec 6

PMID 19057022

Citations 9

Authors

Authors

Huan Wang

Rong Tang

Weiyu Zhang

Karine Amirikian

Zhen Geng

Jianguo Geng

Robert P Hebbel

Lijun Xia

Jamey D Marth

Minoru Fukuda

Shigeki Katoh

Yuqing Huo

Affiliations

Affiliations

Soon will be listed here.

Abstract

Objective: Core2 1-6-N-glucosaminyltransferase-I (C2GlcNAcT-I) modification of adhesion molecules is required for optimal binding to target ligands. The objective of this study was to determine the role of C2GlcNAcT-I in the recruitment of Ly-6C(hi) monocytes to atherosclerotic lesions and in lesion formation in mice.

Methods And Results: In a whole-blood binding assay, Ly-6C(hi) monocytes and certain lymphocytes and natural killer cells from wild-type mice bound to P- and E-selectin. C2GlcNAcT-I deficiency abrogated leukocyte binding to P- and E-selectin in this assay as well as in an in vitro flow chamber assay. Moreover, C2GlcNAcT-I deficiency decreased Ly-6C(hi) monocyte interactions with atherosclerotic arteries under physiological flow conditions and also inhibited monocyte recruitment to the peritoneal cavity in mice challenged with thioglycollate. In apolipoprotein E-deficient (apoE(-/-)) mice, lack of C2GlcNAcT-I resulted in fewer and smaller atherosclerotic lesions in mouse aortas. Atherosclerosis was also suppressed in C2GlcNAcT-I(-/-)/apoE(-/-) chimeric mice transplanted with C2GlcNAcT-I(+/+) bone marrow cells.

Conclusions: C2GlcNAcT-I in both leukocytes and blood vessel wall cells contributes to leukocyte recruitment to the arterial wall. C2GlcNAcT-I deficiency leads to the formation of small, macrophage-poor, and collagen-rich atherosclerotic lesions.

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