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 Citations (Scopus)

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

Fingerprint

Apolipoproteins E
Monocytes
Leukocytes
P-Selectin
E-Selectin
Thioglycolates
Peritoneal Cavity
Natural Killer Cells
Bone Marrow Cells
Cell Wall
Blood Vessels
Aorta
Atherosclerosis
Collagen
Arteries
Macrophages
Lymphocytes
Ligands

Keywords

  • Adhesion molecule
  • Atherosclerosis
  • Monocyte

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Core2 1-6-N-glucosaminyltransferase-i is crucial for the formation of atherosclerotic lesions in apolipoprotein E-deficient mice. / Wang, Huan; Tang, Rong; Zhang, Weiyu; Amirikian, Karine; Geng, Zhen; Geng, Jianguo; Hebbel, Robert P.; Xia, Lijun; Marth, Jamey D.; Fukuda, Minoru; Katoh, Shigeki; Huo, Yuqing.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 29, No. 2, 01.02.2009, p. 180-187.

Research output: Contribution to journalArticle

Wang, Huan ; Tang, Rong ; Zhang, Weiyu ; Amirikian, Karine ; Geng, Zhen ; Geng, Jianguo ; Hebbel, Robert P. ; Xia, Lijun ; Marth, Jamey D. ; Fukuda, Minoru ; Katoh, Shigeki ; Huo, Yuqing. / Core2 1-6-N-glucosaminyltransferase-i is crucial for the formation of atherosclerotic lesions in apolipoprotein E-deficient mice. In: Arteriosclerosis, thrombosis, and vascular biology. 2009 ; Vol. 29, No. 2. pp. 180-187.
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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.",
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AU - Wang, Huan

AU - Tang, Rong

AU - Zhang, Weiyu

AU - Amirikian, Karine

AU - Geng, Zhen

AU - Geng, Jianguo

AU - Hebbel, Robert P.

AU - Xia, Lijun

AU - Marth, Jamey D.

AU - Fukuda, Minoru

AU - Katoh, Shigeki

AU - Huo, Yuqing

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N2 - 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.

AB - 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.

KW - Adhesion molecule

KW - Atherosclerosis

KW - Monocyte

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