title: Low dose aspirin is associated with plasma chemerin levels and may reduce adipose tissue inflammation.
abstract: Chemerin is a peptide chemoattractant for macrophages and an adipokine regulating adipocyte differentiation and metabolism. Plasma chemerin is increased in chronic inflammatory diseases and in obesity. As inflammation and obesity are risk factors for coronary artery disease (CAD), we investigated possible associations of plasma chemerin with inflammatory markers and atherosclerosis in a CAD case-control study (n=470). Chemerin levels were associated with C-reactive protein, BMI and LDL levels, and negatively associated with HDL levels. Mean plasma chemerin levels were similar in controls and CAD patients but significantly higher in CAD patients not taking low dose aspirin. To investigate the mechanism of chemerin reduction by aspirin, we analyzed chemerin expression in hepatocytes and adipocytes treated with aspirin in the presence and absence of inflammatory cytokines. Chemerin expression was upregulated by pro-inflammatory stimuli in adipocytes but not in hepatocytes. Treatment of stimulated hepatocytes and adipocytes with aspirin did not affect chemerin expression. However, treatment of inflammatory M1 macrophages with aspirin reduced secretion of the pro-inflammatory cytokines IL-1β and IL-6, and increased secretion of the anti-inflammatory IL-10. In summary, we show that plasma chemerin levels are associated with markers of inflammation and that they are significantly higher in CAD patients not treated with low dose aspirin. In addition, we show that low dose aspirin treatment reduces pro-inflammatory cytokine secretion by macrophages, which may lead to reduced chemerin secretion by adipocytes and may be a reason for the lower chemerin levels in the circulation of CAD patients on low dose aspirin.
authors.affiliation: Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland; Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Herová
authors.affiliation: Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland; Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Mattia
authors.initials: M
authors.lastname: Schmid
authors.affiliation: Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Gemperle
authors.affiliation: Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: Christa
authors.initials: C
authors.lastname: Loretz
authors.affiliation: Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland; Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland. Electronic address: martin.hersberger@kispi.uzh.ch.
authors.forename: Martin
authors.initials: M
authors.lastname: Hersberger
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000473:pathology*; D001241:Aspirin / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male
chemical_list: D015415:Biomarkers; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; C478630:RARRES2 protein, human; D016753:Interleukin-10; D001241:Aspirin
keywords: Adipose tissue inflammation; Chemerin; Coronary artery disease; Obesity