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 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.
Inoue
Michihiko
M
Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan.
Ishida
Tatsuro
T
Yasuda
Tomoyuki
T
Toh
Ryuji
R
Hara
Tetsuya
T
Cangara
Husni M
HM
Rikitake
Yoshiyuki
Y
Taira
Kazuki
K
Sun
Li
L
Kundu
Ramendra K
RK
Quertermous
Thomas
T
Hirata
Ken-ichi
K
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D020868:Gene Silencing; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D014651:Vasa Vasorum / Q000378:metabolism / Q000473:pathology / Q000502:physiology
D015815:Cell Adhesion Molecules; C428190:Esam protein, mouse; D034741:RNA, Small Interfering