Resistin-Like Molecule Is Abundantly Expressed in Foam Cells and Is Involved in Atherosclerosis Development

被引：35

作者：

Kushiyama, Akifumi ^{[1
]}

Sakoda, Hideyuki ^{[2
]}

Oue, Naohide ^{[5
]}

Okubo, Masamichi ^{[6
]}

Nakatsu, Yusuke ^{[6
]}

Ono, Haruya ^{[6
]}

Fukushima, Toshiaki ^{[6
]}

Kamata, Hideaki ^{[6
]}

Nishimura, Fusanori ^{[7
]}

Kikuchi, Takako ^{[1
]}

Fujishiro, Midori ^{[2
]}

Nishiyama, Koichi ^{[3
]}

Aburatani, Hiroyuki ^{[4
]}

Kushiyama, Sakura ^{[1
,3
]}

Iizuka, Masaki ^{[8
]}

Taki, Naoyuki ^{[8
]}

Encinas, Jeffrey ^{[8
]}

Sentani, Kazuhiro ^{[5
]}

Ogonuki, Narumi ^{[9
]}

Ogura, Atsuo ^{[9
]}

Kawazu, Shoji

Yasui, Wataru ^{[5
]}

Higashi, Yukihito ^{[6
]}

Kurihara, Hiroki ^{[3
]}

Katagiri, Hideki ^{[10
]}

Asano, Tomoichiro ^{[6
]}

机构：

[1] Asahi Life Fdn, Inst Adult Dis, Dept Internal Med, Tokyo, Japan

[2] Univ Tokyo, Grad Sch Med, Dept Internal Med, Tokyo, Japan

[3] Univ Tokyo, Grad Sch Med, Dept Physiol Chem & Metab, Tokyo, Japan

[4] Univ Tokyo, Res Ctr Adv Sci & Technol, Tokyo, Japan

[5] Hiroshima Univ, Grad Sch Biomed Sci, Dept Mol Pathol, Hiroshima 7348551, Japan

[6] Hiroshima Univ, Grad Sch Biomed Sci, Div Mol Med Sci, Dept Med Chem, Hiroshima 7348551, Japan

[7] Hiroshima Univ, Grad Sch Biomed Sci, Dept Dent Sci Hlth Promot, Div Cervicognathostomatol, Hiroshima 7348551, Japan

[8] Nippon Boehringer Ingelheim Co Ltd, Kobe Pharma Res Inst, Dept Mol & Cellular Biol, Kobe, Hyogo, Japan

[9] RIKEN, BioResource Ctr, Tsukuba, Ibaraki, Japan

[10] Tohoku Univ, Grad Sch Med, Div Mol Metab & Diabet, Sendai, Miyagi 980, Japan

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2013年 / 33卷 / 08期

基金：

日本学术振兴会;

关键词：

atherosclerosis; inflammation; macrophage; PLASMA RESISTIN; RELM-BETA; MURINE; RELM-BETA/FIZZ2; INFLAMMATION; MACROPHAGES; INNATE; MICE;

D O I：

10.1161/ATVBAHA.113.301546

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective Resistin-like molecule (RELM) is a secretory protein homologous to resistin and reportedly contributes to local immune response regulation in gut and bronchial epithelial cells. However, we found that activated macrophages also express RELM and thus investigated the role of RELM in the development of atherosclerosis. Approach and Results It was demonstrated that foam cells in atherosclerotic lesions of the human coronary artery abundantly express RELM. RELM knockout ((-/-)) and wild-type mice were mated with apolipoprotein E-deficient background mice. RELM-/- apolipoprotein E-deficient mice exhibited less lipid accumulation in the aortic root and wall than RELM+/+ apolipoprotein E-deficient mice, without significant changes in serum lipid parameters. In vitro, RELM-/- primary cultured peritoneal macrophages (PCPMs) exhibited weaker lipopolysaccharide-induced nuclear factor-B classical pathway activation and inflammatory cytokine secretion than RELM+/+, whereas stimulation with RELM upregulated inflammatory cytokine expressions and increased expressions of many lipid transporters and scavenger receptors in PCPMs. Flow cytometric analysis revealed inflammatory stimulation-induced RELM in F4/80(+) CD11c(+) PCPMs. In contrast, the expressions of CD11c and tumor necrosis factor were lower in RELM-/- PCPMs, but both were restored by stimulation with recombinant RELM. Conclusions RELM is abundantly expressed in foam cells within plaques and contributes to atherosclerosis development via lipid accumulation and inflammatory facilitation.

引用

页码：1986 / 1993

页数：8

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