sdLDL降低冠状动脉狭窄患者分化的m2 -巨噬细胞MRC1表达水平和组胺e分泌

Amene Yarnazari, Parisa Hassanpour, Syed Reza Hosseini-Fard, Abdollah Amirfarhangi, M. Najafi
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引用次数: 7

摘要

巨噬细胞极化被认为参与了动脉粥样硬化斑块的初始事件和重塑。甘露糖受体C型1 (MRC1)是一种参与吞噬作用的跨膜糖蛋白,在M2巨噬细胞中高表达。目的探讨小密度低密度脂蛋白(sdLDL)对冠状动脉狭窄患者和健康人单核细胞分化的M2巨噬细胞MRC1基因表达水平和组胺分泌的影响。方法采用RosetteSep试剂盒分离健康人(< 5%狭窄)和狭窄患者(> 70%狭窄)、SVD(单血管病)、2VD(双血管病)和3VD(三血管病)的单核细胞,通过巨噬细胞集落刺激因子(M-CSF)分化为M2巨噬细胞。采用聚乙二醇联合沉淀法得到sdLDL颗粒。RT-qPCR检测MRC1基因表达,ELISA检测组胺水平。结果sdLDL治疗后,健康人M2巨噬细胞中MRC1基因表达水平显著升高(P=0.05),而SVD (P=0.05)、2VD (P=0.01)和3VD (P=0.9)患者M2巨噬细胞中MRC1基因表达水平明显降低。与健康对照组相比,患者M2巨噬细胞分泌的组胺值(7 d)高于对照组(>3倍,P=0.02)。结论sdLDL颗粒可降低冠状动脉病变患者M2巨噬细胞中MRC1基因表达水平。此外,它们具有较高的组胺分泌炎症能力。
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The sdLDL Reduces MRC1 Expression Level and Secretion of Histamin e in Differentiated M2-macrophages from Patients with Coronary Artery Stenosis.
BACKGROUND The macrophage polarization is proposed to be involved in initial events and remodeling of atherosclerosis plaques. Mannose receptor, C type 1 (MRC1) is a trans-membrane glycoprotein participating in phagocytosis and, is highly expressed in the M2 macrophages. OBJECTIVE The aim of this study was to investigate the effects of sdLDL (small dense LDL) on the MRC1 gene expression level and secretion of histamine in the differentiated M2 macrophages from monocytes of patients with coronary artery stenosis and healthy subjects. METHOD The monocytes were isolated from healthy subjects (< 5% stenosis) and patients (> 70% stenosis, SVD (Single Vessel Disease), 2VD (Two-Vessel Disease) and 3VD (Three-Vessel Disease)) by RosetteSep kit and, were differentiated into M2 macrophages by macrophage colonystimulating factor (M-CSF). The sdLDL particles were obtained by PEG-combined precipitation method. The MRC1 gene expression and histamine levels were measured by RT-qPCR and ELISA techniques, respectively. RESULTS The MRC1 gene expression level was significantly increased in M2 macrophages of healthy subjects (P=0.05) while it reduced in SVD (P=0.05), 2VD (P=0.01) and 3VD (P=0.9) patients after treatment with sdLDL. The histamine value secreted from M2 macrophages (7-day) was higher (>3-fold, P=0.02) in patients as compared to healthy controls. CONCLUSION The results showed that the sdLDL particles reduce the MRC1 gene expression levels in the differentiated M2 macrophages from patients with coronary artery disease. Furthermore, they had high inflammatory capacity for the secretion of histamine.
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