Herová Magdalena, Schmid Mattia, Gemperle Claudio, Loretz Christa, Hersberger Martin
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.
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.
Atherosclerosis. 2014 Aug;235(2):256-62. doi: 10.1016/j.atherosclerosis.2014.05.912. Epub 2014 May 15.
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.
瑞连蛋白是一种巨噬细胞肽趋化因子，也是一种调节脂肪细胞分化和代谢的脂肪因子。在慢性炎症性疾病和肥胖症中，血浆瑞连蛋白水平会升高。由于炎症和肥胖是冠状动脉疾病（CAD）的危险因素，我们在一项CAD病例对照研究（n = 470）中调查了血浆瑞连蛋白与炎症标志物和动脉粥样硬化之间的可能关联。瑞连蛋白水平与C反应蛋白、体重指数和低密度脂蛋白水平相关，与高密度脂蛋白水平呈负相关。对照组和CAD患者的平均血浆瑞连蛋白水平相似，但未服用低剂量阿司匹林的CAD患者的血浆瑞连蛋白水平显著更高。为了研究阿司匹林降低瑞连蛋白水平的机制，我们分析了在有或没有炎性细胞因子存在的情况下，用阿司匹林处理的肝细胞和脂肪细胞中瑞连蛋白的表达。炎性刺激会使脂肪细胞中的瑞连蛋白表达上调，但不会使肝细胞中的瑞连蛋白表达上调。用阿司匹林处理受刺激的肝细胞和脂肪细胞不会影响瑞连蛋白的表达。然而，用阿司匹林处理炎性M1巨噬细胞会减少促炎细胞因子白细胞介素-1β和白细胞介素-6的分泌，并增加抗炎细胞因子白细胞介素-10的分泌。总之，我们发现血浆瑞连蛋白水平与炎症标志物相关，且在未接受低剂量阿司匹林治疗的CAD患者中显著更高。此外，我们发现低剂量阿司匹林治疗可减少巨噬细胞促炎细胞因子的分泌，这可能导致脂肪细胞瑞连蛋白分泌减少，这可能是服用低剂量阿司匹林的CAD患者循环中瑞连蛋白水平较低的原因。
