Resistin-like molecule β is abundantly expressed in foam cells and is involved in atherosclerosis development

Akifumi Kushiyama, Hideyuki Sakoda, Naohide Oue, Masamichi Okubo, Yusuke Nakatsu, Haruya Ono, Toshiaki Fukushima, Hideaki Kamata, Fusanori Nishimura, Takako Kikuchi, Midori Fujishiro, Koichi Nishiyama, Hiroyuki Aburatani, Sakura Kushiyama, Masaki Iizuka, Naoyuki Taki, Jeffrey Encinas, Kazuhiro Sentani, Narumi Ogonuki, Atsuo OguraShoji Kawazu, Wataru Yasui, Yukihito Higashi, Hiroki Kurihara, Hideki Katagiri, Tomoichiro Asano

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28 Citations (Scopus)

Abstract

OBJECTIVE - : Resistin-like molecule (RELM) β 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 RELMβ and thus investigated the role of RELMβ in the development of atherosclerosis. APPROACH AND RESULTS - : It was demonstrated that foam cells in atherosclerotic lesions of the human coronary artery abundantly express RELMβ. RELMβ knockout ( -/-) and wild-type mice were mated with apolipoprotein E-deficient background mice. RELMβ-/- apolipoprotein E-deficient mice exhibited less lipid accumulation in the aortic root and wall than RELMβ+/+ apolipoprotein E-deficient mice, without significant changes in serum lipid parameters. In vitro, RELMβ-/- primary cultured peritoneal macrophages (PCPMs) exhibited weaker lipopolysaccharide- induced nuclear factor-κB classical pathway activation and inflammatory cytokine secretion than RELMβ+/+, whereas stimulation with RELMβ upregulated inflammatory cytokine expressions and increased expressions of many lipid transporters and scavenger receptors in PCPMs. Flow cytometric analysis revealed inflammatory stimulation-induced RELMβ in F4/80(+) CD11c(+) PCPMs. In contrast, the expressions of CD11c and tumor necrosis factor were lower in RELMβ-/- PCPMs, but both were restored by stimulation with recombinant RELMβ. CONCLUSIONS - : RELMβ is abundantly expressed in foam cells within plaques and contributes to atherosclerosis development via lipid accumulation and inflammatory facilitation.

Original languageEnglish
Pages (from-to)1986-1993
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume33
Issue number8
DOIs
Publication statusPublished - Aug 2013

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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    Kushiyama, A., Sakoda, H., Oue, N., Okubo, M., Nakatsu, Y., Ono, H., Fukushima, T., Kamata, H., Nishimura, F., Kikuchi, T., Fujishiro, M., Nishiyama, K., Aburatani, H., Kushiyama, S., Iizuka, M., Taki, N., Encinas, J., Sentani, K., Ogonuki, N., ... Asano, T. (2013). Resistin-like molecule β is abundantly expressed in foam cells and is involved in atherosclerosis development. Arteriosclerosis, thrombosis, and vascular biology, 33(8), 1986-1993. https://doi.org/10.1161/ATVBAHA.113.301546