title: Role of Hic-5 in the formation of microvilli-like structures and the monocyte-endothelial interaction that accelerates atherosclerosis.
abstract: OBJECTIVE
  The adhesion of circulating monocytes to endothelial cells (ECs) is an early and critical event in the formation of atherosclerotic plaques. Hydrogen peroxide-inducible clone 5 (Hic-5) serves as an adaptor molecule in cell adhesion complexes. However, the role of endothelial Hic-5 in monocyte-EC interaction and atherogenesis remains unclear. We examined the roles of endothelial Hic-5 in monocyte-EC interaction and atherogenesis using mouse models of atherosclerosis and cultured human umbilical vein endothelial cells (HUVECs).
  
  
  RESULTS
  Hic-5 was expressed in ECs, but not in monocytes/macrophages. An ex vivo monocyte adhesion assay revealed that adhesion of THP-1 monocytes to aortas isolated from Apoe(-/-) and LDLR(-/-) mice stimulated by TNF-α or oxidized LDL was suppressed by Hic-5 deficiency. Scanning electron microscopic observations of aortas harvested from Apoe(-/-) mice revealed that TNF-α- or oxidized LDL-induced microvilli-like structures were markedly suppressed by Hic-5 deficiency. Relative Hic-5 deficiency suppressed 60% of the atherosclerotic lesions in aortas from Apoe(-/-) and LDLR(-/-) mice. In contrast, overexpression of Hic-5 in HUVECs promoted induction of microvilli-like structures and adherence of THP-1 cells in an adhesion receptor such as intercellular adhesion molecule-1- and vascular cell adhesion molecule-1-dependent manner.
  
  
  CONCLUSIONS
  Hic-5 in ECs plays an important role in the formation of microvilli-like structures and in the interaction between ECs and monocytes, leading to monocyte recruitment and subsequent development of atherosclerosis.
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Shigeko
authors.initials: S
authors.lastname: Arita-Okubo
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan shuri@pharm.showa-u.ac.jp.
authors.forename: Joo-Ri
authors.initials: JR
authors.lastname: Kim-Kaneyama
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Lei
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Wen-Guang
authors.initials: WG
authors.lastname: Fu
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ohnishi
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Miyauchi
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University Koto Toyosu Hospital, Tokyo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Honda
authors.affiliation: Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Itabe
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Miyazaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000648:ultrastructure; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D002448:Cell Adhesion; D002478:Cells, Cultured; D018920:Coculture Techniques; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D060588:LIM Domain Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008871:Microvilli / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C573420:ICAM1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; C490351:TGFB1I1 protein, human; C090090:Tgfb1i1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1
keywords: Atherosclerosis; Endothelial cells; Microvilli-like structures