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不稳定型心绞痛患者的单核细胞表达高水平的趋化因子和模式识别受体。

Monocytes of patients with unstable angina express high levels of chemokine and pattern-recognition receptors.

机构信息

Department of Clinical Pathology, School of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

Department of Clinical Pathology, School of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil; Federal University of Ceará (UFC), Fortaleza, Ceará, Brazil; University of Fortaleza (UNIFOR), Fortaleza, Ceará, Brazil.

出版信息

Cytokine. 2019 Jan;113:61-67. doi: 10.1016/j.cyto.2018.06.008. Epub 2018 Jun 20.

Abstract

BACKGROUND AND AIMS

Macrophages derived from monocytes play an important role in atherosclerosis progression. Subpopulations of circulating classical, intermediate, and non-classical monocytes possess distinct functions and phenotypes, and participate in the pathogenesis of disease. The aim of this study was to compare the quantity and phenotypes of circulating monocyte subpopulations in patients with established atherosclerosis and healthy control individuals. Additionally, the study aimed to provide insight into the functional activity of monocytes against a heat shock protein (HSP60).

METHODS

Chemokine and pattern recognition receptors in monocyte subsets obtained from peripheral blood of acute and chronic coronary artery disease patients and controls were quantified by flow cytometry. Furthermore, monocytes from healthy controls were stimulated in vitro with HSP60, and the cytokines produced by them were evaluated by flow cytometry.

RESULTS

Eighteen controls (C), 34 individuals with risk factors for cardiovascular disease (RF), 32 patients with stable angina (SA), and 16 patients with unstable angina (UA) were enrolled in the study. The absolute count of intermediate monocytes was found to be increased in patients of the UA group; high frequencies of the chemokine receptors CCR2, CCR5, and CX3CR1 were also observed in this subpopulation. Moreover, the pattern recognition receptors TLR2 and TLR4 were more frequent in intermediate monocytes from the UA group. Furthermore, the intermediate monocytes from healthy individuals produced IL-12p70 after stimulation with HSP60.

CONCLUSIONS

Our results show that intermediate monocytes of UA patients exhibited an enhanced expression of the receptors involved in the recognition of damage-associated molecular patterns (DAMPs) and enhancement of the migratory function. Hence, they might contribute to the propagation and progression of inflammation observed in atherosclerosis, especially in the acute setting.

摘要

背景与目的

单核细胞衍生的巨噬细胞在动脉粥样硬化进展中发挥重要作用。循环中的经典型、中间型和非经典型单核细胞亚群具有不同的功能和表型,并参与疾病的发病机制。本研究旨在比较已确诊动脉粥样硬化患者和健康对照个体循环单核细胞亚群的数量和表型。此外,本研究旨在深入了解单核细胞针对热休克蛋白 (HSP60) 的功能活性。

方法

通过流式细胞术定量检测急性和慢性冠状动脉疾病患者和对照组外周血中单核细胞亚群的趋化因子和模式识别受体。此外,体外刺激健康对照组的单核细胞,并通过流式细胞术评估它们产生的细胞因子。

结果

本研究纳入了 18 名对照者(C)、34 名心血管疾病危险因素患者(RF)、32 名稳定性心绞痛患者(SA)和 16 名不稳定型心绞痛患者(UA)。结果发现,UA 组患者中间型单核细胞的绝对计数增加;该亚群中还观察到趋化因子受体 CCR2、CCR5 和 CX3CR1 的高频率。此外,UA 组中间型单核细胞中 TLR2 和 TLR4 模式识别受体的频率也更高。此外,健康个体的中间型单核细胞在受到 HSP60 刺激后会产生 IL-12p70。

结论

我们的研究结果表明,UA 患者的中间型单核细胞表现出参与识别损伤相关分子模式(DAMPs)的受体表达增强,并增强了迁移功能。因此,它们可能有助于动脉粥样硬化中炎症的传播和进展,尤其是在急性阶段。

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