趋化因子促进冠状动脉粥样硬化斑块不稳定的分子机制

Roles of monocyte chemoattractant protein-1, RANTES and Fractalkine on promoting vulnerability of atherosclerotic plaques

目的研究单核细胞趋化因子在动脉粥样硬化斑块不稳定中作用的分子机制。方法对50例稳定性心绞痛（SAP）和50例不稳定性心绞痛（UAP）患者分别进行冠状动脉造影（CAG）和血管内超声（IVUS）检查。应用Transwell小室检测2组患者血单核细胞的趋化活性，ELISA法检测血清中高敏C反应蛋白（hs．CRP）、单核细胞趋化蛋白-1（MCP—1）、T细胞表达和分泌因子（RANTES）和Fractalkine的水平，用实时PCR检测单核细胞中MCP-1、RANTES和Fractalkine的mRNA表达水平。结果IVUS共检出SAP组85处斑块，UAP组90处斑块，其中，UAP组主要为脂质性斑块48％（43／90），而SAP组主要为纤维性斑块54％（46／85），脂质斑块仅占16％（14／85）。与SAP组比较，UAP组斑块负荷和血管重构指数明显大于前者（P均〈0．01）。UAP组单核细胞趋化活性明显增强，单核细胞移动数量明显多于SAP组，两组比较差异有统计学意义（P〈0．01）。UAP组血清中hs—CRP、MCP-1、RANTES和Fractalkine水平明显高于SAP组（P〈0．05或P〈0．01）。UAP组MCP-1、RANTES和Fractalkine的mRNA表达水平明显高于SAP组（P〈0．05）。结论单核细胞趋化因子MCP-1、RANTES和Fractalkine可能促进了冠状动脉粥样硬化斑块的不稳定。

Objective To elucidate the roles of monocyte chemotactic factors （MCP-1, RANTES and Fractalkine） on the vulnerability of atherosclerotic plaques in patients with stable （SAP） and unstable angina pectoris （UAP）. Methods Patients with SAP （n = 50） and UAP （n = 50） underwent coronary angiography （CAG） and intravenous ultrasound （IVUS） were included in the study. Monocyte chemotaxis was assayed by the transwell chamber. Concentrations of hs-CRP, MCP-1, RANTES and Fractalkine were measured by Enzyme-linked-immonosorbent assay （ELISA）. mRNA expression of MCP-1, RANTES and Fractalkine in the monocytes was detected by RT-PCR. Results IVUS evidenced soft lipid plaques in 48% UAP patients and in 16% SAP patients （P 〈 0. 05 ）. SAP patients had mainly fibrous and mixed plaques. Plaque burden and vascular remodeling index were significantly higher in UAP patients than in SAP patients （P 〈0. 01）. The averaged number of migrated monocytes in the UAP patients were higher than that in patients with SAP （P 〈 O. 01 ）. Concentration of hs-CRP, MCP-1, RANTES and Fractalkine were significantly higher in UAP patients than those of SAP patients （P 〈0. 05 or P 〈0. 01 ）. mRNA expression of MCP-1, RANTES and Fractalkine in patients with UAP was significantly higher than those of SAP patients （P 〈 0. 05）. Conclusion Upregnlated monocyte chemotactic factors （ MCP-1, RANTES and Fractalkine） might promote coronary plaque vulnerability in UAP patients.