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

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

Comparison of RELMα and RELMβ Single- and Double-Gene-Deficient Mice Reveals that RELMα Expression Dictates Inflammation and Worm Expulsion in Hookworm Infection

“…However, we previously showed that RELM␣ preferentially bound CD4 ϩ T cells and not B cells (12), so it is more likely that the RELM␣-mediated effects are through CD4 ϩ T cells. Although intestinal epithelial cells are the main cellular source of murine RELM␤, recent human studies have shown that bronchial epithelial cells in the lung and activated macrophages can express high levels of human RELM␤ (35,36), which fits the expression pattern of mouse RELM␣. In our studies, we found that both RELM␣ and RELM␤ were significantly upregulated and maintained in the lung and intestine following N. brasiliensis in- fection.…”

Relationships between Serum Resistin and Fat Intake, Serum Lipid Concentrations and Adiposity in the General Population

“…We therefore suggest that this dietary pattern, which is characterized by the intake of foods rich in saturated fat and poor in monounsaturated fat, favors the induction of inflammation and stimulates the production of resistin. In contrast, the Mediterranean diet, which is low in saturated fat and rich in monounsaturated fat, inflammation, the serum lipid levels are often decreased, possibly in relation to the accumulation of lipids in macrophages as a result of the actions of resistin 29) . This view is compatible with the observation of elevated resistin levels in patients with inflammatory diseases, such as rheumatoid arthritis, as the onset of arthritis is known to be preceded by a decrease in the levels of serum lipids 38) and an increase in the levels of proinflammatory cytokines 39) .…”

“…We also found that the resistin level is associated with the non-HDL cholesterol level, a finding not previously reported in the literature. The inverse relationship between resistin and cholesterol can be attributed, at least in part, to the ability of resistin to sequester serum lipids and store them in macrophages 29) . However, the actions of HDL cholesterol counteract the effects of resistin, as the former has anti-inflammatory properties 30,31) and is able to decrease the lipid serum total cholesterol and its HDL and LDL fractions.…”

The adipokine Retnla modulates cholesterol homeostasis in hyperlipidemic mice

“…Retnla is expressed mainly by hematopoietic cells and stromal vascular cells but not by adipocytes in WAT 12,37,43,44 . Retnlb is expressed abundantly in the colon in both mouse and human, and expression can also be induced in macrophages under the proper inflammatory conditions 12,44,45 . In mice, resistin is primarily produced in adipocytes, whereas in humans, resistin is mainly derived from monocytes and macrophages 19,46 .…”

“…Faecal bile acid excretion (μmol per day per 100 g body weight) ARTICLE family members, Retnlb and resistin are implicated as mediators of inflammation 46,56,57 and abundantly expressed in macrophages of atheroma involved in atherosclerosis development 45,58 13,18 , while in a model of chronic inflammation by Schistosoma mansoni infection, both the lung inflammation and liver fibrosis were increased by Retnla deficiency via an enhanced Th2 immune responses 36,37 . These results suggest that the beneficial and detrimental roles of Retnla in inflammatory diseases are likely influenced by the type of immune stimulus, the duration of the stimulus exposure and the tissue type.…”