Endothelial cell-selective adhesion molecule modulates atherosclerosis through plaque angiogenesis and monocyte–endothelial interaction

Endothelial cell-selective adhesion molecule (ESAM) is a new member of the immunoglobulin superfamily, which is expressed in vascular endothelial cells. Previous studies have demonstrated that ESAM regulates angiogenesis, endothelial permeability, and leukocyte transmigration. However, little is kno...

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Bibliographic Details
Published in:Microvascular research 2010-09, Vol.80 (2), p.179-187
Main Authors: Inoue, Michihiko, Ishida, Tatsuro, Yasuda, Tomoyuki, Toh, Ryuji, Hara, Tetsuya, Cangara, Husni M., Rikitake, Yoshiyuki, Taira, Kazuki, Sun, Li, Kundu, Ramendra K., Quertermous, Thomas, Hirata, Ken-ichi
Format: Article
Language:English
Subjects:
Adhesion molecule
Angiogenesis
Animals
Aorta - metabolism
Aorta - pathology
Atherosclerosis
Atherosclerosis - metabolism
Atherosclerosis - pathology
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cell Line
Cell Movement
Disease Models, Animal
Endothelial Cells - metabolism
Endothelial Cells - pathology
Endothelium
Endothelium, Vascular - metabolism
Endothelium, Vascular - pathology
Gene Silencing
Humans
Macrophage
Macrophages - metabolism
Macrophages - pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Monocyte
Monocytes - metabolism
Monocytes - pathology
Neovascularization, Pathologic - metabolism
Neovascularization, Pathologic - pathology
Neovascularization, Pathologic - physiopathology
RNA, Small Interfering - genetics
Transfection
Vasa vasorum
Vasa Vasorum - metabolism
Vasa Vasorum - pathology
Vasa Vasorum - physiology
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Summary:Endothelial cell-selective adhesion molecule (ESAM) is a new member of the immunoglobulin superfamily, which is expressed in vascular endothelial cells. Previous studies have demonstrated that ESAM regulates angiogenesis, endothelial permeability, and leukocyte transmigration. However, little is known concerning the role of ESAM in atherosclerosis. In this study, we assessed the effects of ESAM inactivation on atherosclerosis in mice. ESAM−/− mice were bred with apoE−/− mice to generate double knockout mice, and the aortic lesion size of apoE−/− and ESAM−/− apoE−/− mice was compared histologically. Although plasma cholesterol levels were higher in ESAM−/− apoE−/− mice, the lesion size was markedly smaller than in apoE−/− mice. ESAM−/− apoE−/− mice exhibited a decrease in the number of vasa vasorum and macrophages in the vessel wall. In vitro adhesion assays showed that THP-1 cells, which did not express ESAM, bound to the ESAM-coated culture plates, suggesting that ESAM may interact with heterophilic ligand(s) on monocytes. Moreover, downregulation of ESAM by siRNA in the endothelial monolayer diminished transendothelial migration of THP-1 cells. In conclusion, ESAM inactivation can reduce susceptibility to atherosclerosis by inhibiting plaque neovascularization and macrophage infiltration into the atheroma.
ISSN:0026-2862
1095-9319
DOI:10.1016/j.mvr.2010.04.005