Core2 1-6-N-glucosaminyltransferase-i is crucial for the formation of atherosclerotic lesions in apolipoprotein E-deficient mice

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

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Objective - Core2 1-6-N-glucosaminyltransferase-I (C2G1cNAcT-I) modification of adhesion molecules is required for optimal binding to target ligands. The objective of this study was to determine the role of C2G1cNAcT-I in the recruitment of Ly-6Chi monocytes to atherosclerotic lesions and in lesion formation in mice. Methods and Results - In a whole-blood binding assay, Ly-6Chi monocytes and certain lymphocytes and natural killer cells from wild-type mice bound to P- and E-selectin. C2G1cNAcT-I deficiency abrogated leukocyte binding to P- and E-selectin in this assay as well as in an in vitro flow chamber assay. Moreover, C2G1cNAcT-I deficiency decreased Ly-6Chi 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 C2G1cNAcT-I resulted in fewer and smaller atherosclerotic lesions in mouse aortas. Atherosclerosis was also suppressed in C2G1cNAcT-I-/-/apoE-/- chimeric mice transplanted with C2G1cNAcT-I+/+ bone marrow cells. Conclusions - C2G1cNAcT-I in both leukocytes and blood vessel wall cells contributes to leukocyte recruitment to the arterial wall. C2G1cNAcT-I deficiency leads to the formation of small, macrophage-poor, and collagen-rich atherosclerotic lesions.

Original languageEnglish (US)
Pages (from-to)180-187
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume29
Issue number2
DOIs
StatePublished - Feb 1 2009
Externally publishedYes

Keywords

  • Adhesion molecule
  • Atherosclerosis
  • Monocyte

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Wang, H., Tang, R., Zhang, W., Amirikian, K., Geng, Z., Geng, J., Hebbel, R. P., Xia, L., Marth, J. D., Fukuda, M., Katoh, S., & Huo, Y. (2009). Core2 1-6-N-glucosaminyltransferase-i is crucial for the formation of atherosclerotic lesions in apolipoprotein E-deficient mice. Arteriosclerosis, thrombosis, and vascular biology, 29(2), 180-187. https://doi.org/10.1161/ATVBAHA.108.170969