Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, is elevated in coronary artery disease and is reduced during statin therapy
Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, is elevated in coronary artery disease and is reduced during statin therapy
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DOI：
10.1161/01.atv.0000190672.36490.7b
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发表时间：
2005-12-01
影响因子：
8.7
通讯作者：
Quehenberger, O
中科院分区：
文献类型：
--
作者：
Damås, JK;Boullier, A;Quehenberger, O
目的-最近的数据主要来自动物模型的研究表明，fractalkine（CX 3CL 1）及其同源受体CX 3CR 1在动脉粥样硬化形成中发挥作用。因此，我们假设CX 3CL 1/CX 3CR 1表达增强可能促进冠状动脉疾病（CAD）患者的动脉粥样硬化形成。方法和结果-我们检测了不同CAD人群外周血单核细胞（PBMC）中CX 3CL 1和CX 3CR 1表达的血浆水平（30例既往心肌梗死患者，40例稳定型心绞痛患者，40例不稳定型心绞痛患者，和总共35个对照），并使用各种实验方法来表征CX 3CL 1介导的白细胞应答。我们发现，血浆中CX 3CL 1水平在CAD中大大增加，特别是在不稳定的疾病中。PBMC中CX 3CR 1表达的平行增加主要归因于CX 3CR 1（+）CD 3（+）CD 8（+）T细胞亚群的扩增，并与对CX 3CL 1的趋化性、粘附性和炎症反应增强相关。他汀类药物治疗6个月降低了CX 3CL 1和CX 3CR 1的表达，仅在侵袭性（阿托伐他汀，80 mg qd）而非常规（辛伐他汀，20 mg qd）治疗期间两个参数达到统计学显著性。因此，PBMC对CX 3CL 1的功能反应，包括迁移，粘附和白细胞介素-8的分泌减弱的treatment.Conclusion -我们的研究结果表明，CX 3CL 1/CX 3CR 1二联体可能有助于动脉粥样硬化和斑块不稳定在人类CAD。
Objective - Recent data derived primarily from studies in animal models suggest that fractalkine (CX3CL1) and its cognate receptor, CX3CR1, play a role in atherogenesis. We, therefore, hypothesized that enhanced CX3CL1/CX3CR1 expression may promote atherogenesis in patients with coronary artery disease (CAD).Methods and Results - We examined the plasma levels of CX3CL1 and CX3CR1 expression in peripheral blood mononuclear cells (PBMC) in various CAD populations (30 patients with previous myocardial infarction, 40 patients with stable angina, 40 patients with unstable angina, and a total of 35 controls) and used various experimental approaches to characterize CX3CL1-mediated leukocyte responses. We found that the plasma levels of CX3CL1 are greatly increased in CAD, particularly in unstable disease. The parallel increase of CX3CR1 expression in PBMC was predominantly attributable to an expansion of the CX3CR1(+)CD3(+)CD8(+) T cell subset and was associated with enhanced chemotactic, adhesive, and inflammatory responses to CX3CL1. Statin therapy for 6 months reduced the expression of CX3CL1 and CX3CR1, reaching statistical significance for both parameters only during aggressive (atorvastatin, 80 mg qd) but not conventional (simvastatin, 20 mg qd) therapy. Consequently, the functional responses of the PBMC to CX3CL1 including migration, adhesion, and secretion of interleukin-8 were attenuated by the treatments.Conclusion - Our results suggest that the CX3CL1/CX3CR1 dyad may contribute to atherogenesis and plaque destabilization in human CAD.