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

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.