ライ ショウホウ   RAI Shouho
  雷 小峰
   所属   埼玉医科大学  医学部 国際医療センター 皮膚科(皮膚腫瘍科)
   職種   助教
論文種別 学術雑誌(原著)
言語種別 英語
査読の有無 査読あり
表題 Role of Hic-5 in the formation of microvilli-like structures and the monocyte-endothelial interaction that accelerates atherosclerosis
掲載誌名 正式名:CARDIOVASCULAR RESEARCH
ISSNコード:0008-6363/1755-3245
出版社 OXFORD UNIV PRESS
巻・号・頁 105(3),361-371頁
著者・共著者 Shigeko Arita-Okubo,Joo-ri Kim-Kaneyama,Xiao-Feng Lei,Wen-Guang Fu,Koji Ohnishi,Motohiro Takeya,Aya Miyauchi,Hirokazu Honda,Hiroyuki Itabe,Takuro Miyazaki,Akira Miyazaki
発行年月 2015/03
概要 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).
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-alpha or oxidized LDL was suppressed by Hic-5 deficiency. Scanning electron microscopic observations of aortas harvested from Apoe(-/-) mice revealed that TNF-alpha- 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.
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.
DOI 10.1093/cvr/cvv003
PMID 25587044