New Insight into Atherosclerosis in Hemodialysis Patients: Overexpression of Scavenger Receptor and Macrophage Colony-Stimulating Factor Genes.

New Insight into Atherosclerosis in Hemodialysis Patients: Overexpression of Scavenger Receptor and Macrophage Colony-Stimulating Factor Genes.
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DOI:
10.1159/000448486
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发表时间:
2016-05
期刊:
影响因子:
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通讯作者:
Nitta K
Nitta K
中科院分区:
其他
文献类型:
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作者:
Nishida M;Ando M;Iwamoto Y;Tsuchiya K;Nitta K

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清道夫受体(SRs)在动脉粥样硬化发生中起关键作用。基于SR基因表达,研究了血液透析(HD)患者特异性动脉粥样硬化的发生机制。采用实时逆转录聚合酶链反应法研究SR-A型和CD36基因在外周血单核细胞中的表达。将HD (n = 30)与年龄匹配的对照组(n = 10)的数据进行比较。采用酶联免疫吸附法检测血清巨噬细胞集落刺激因子(M-CSF)水平,以检测其在SR表达中的作用。两个连续变量之间的统计差异和相关性分别采用Mann-Whitney U检验和Pearson相关系数进行评估。HD患者中SR mrna的相对数量显著高于对照组[中位数(四分位数间距):SR- a, 1.67 (0.96-2.76) vs. 0.90 (0.60-1.04), p = 0.0060;CD36, 1.09(0.88 - -1.74)和0.74 (0.64 - -0.99),p = 0.0255)。HD患者血清M-CSF浓度显著高于对照组[,121(999- 1342)比176 (155-202)pg/ml, p < 0.0001]。此外,HD患者M-CSF mRNA的相对量显著高于对照组[0.79(0.42-1.53)比0.42 (0.28-0.66),p = 0.0392]。40例患者血清M-CSF水平与SR-A mRNA相对含量(r2 = 0.1681, p = 0.0086)和CD36 mRNA相对含量(r2 = 0.1202, p = 0.0284)呈正相关。HD患者易患动脉粥样硬化,这是其单核细胞SR表达增强的结果。SRs和M-CSF是这一高危人群动脉粥样硬化的潜在治疗靶点。
Scavenger receptors (SRs) play a pivotal role in atherogenesis. The mechanism of atherosclerosis, which is specific to hemodialysis (HD) patients, was studied on the basis of SR gene expressions. The gene expressions of SR type A (SR-A) and CD36 were studied in peripheral monocytes by real-time reverse transcription polymerase chain reaction. Data were compared between HD (n = 30) and age-matched control subjects (n = 10). Serum levels of macrophage colony-stimulating factor (M-CSF) were measured with enzyme-linked immunosorbent assay to test its role in SR expression. The statistical differences and associations between two continuous variables were assessed using the Mann-Whitney U test and Pearson's correlation coefficient, respectively. The relative quantities of SR mRNAs were significantly greater in HD patients than in controls [median (interquartile range): SR-A, 1.67 (0.96-2.76) vs. 0.90 (0.60-1.04), p = 0.0060; CD36, 1.09 (0.88-1.74) vs. 0.74 (0.64-0.99), p = 0.0255]. The serum concentration of M-CSF was significantly higher in HD patients than in controls [, 121 (999-1,342) vs. 176 (155-202) pg/ml, p < 0.0001]. In addition, the relative quantity of M-CSF mRNA was significantly greater in HD patients than in controls [0.79 (0.42-1.53) vs. 0.42 (0.28-0.66), p = 0.0392]. The serum M-CSF levels were positively correlated with both the relative quantity of SR-A mRNA (r2 = 0.1681, p = 0.0086) and that of CD36 mRNA (r2 = 0.1202, p = 0.0284) in all subjects (n = 40). HD patients are predisposed to atherosclerosis as a consequence of their enhanced monocyte SR expressions. SRs and M-CSF are potential therapeutic targets for atherosclerosis in this high-risk population.