Arteriosclerosis, thrombosis, and vascular biology · 2013
Resistin-like molecule β is abundantly expressed in foam cells and is involved in atherosclerosis development.
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Kushiyama Akifumi, Sakoda Hideyuki, Oue Naohide, Okubo Masamichi, Nakatsu Yusuke, Ono Haruya, Fukushima Toshiaki, Kamata Hideaki, Nishimura Fusanori, Kikuchi Takako, Fujishiro Midori, Nishiyama Koichi, Aburatani Hiroyuki, Kushiyama Sakura, Iizuka Masaki, Taki Naoyuki, Encinas Jeffrey, Sentani Kazuhiro, Ogonuki Narumi, Ogura Atsuo, Kawazu Shoji, Yasui Wataru, Higashi Yukihito, Kurihara Hiroki, Katagiri Hideki, Asano Tomoichiro
Аннотация
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.
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.