C-C趋化因子配体5（CCL5/调节激活正常T细胞表达和分泌因子）和C-C趋化因子配体18（CCL18/肺和激活调节趋化因子）是难治性不稳定型心绞痛的特异性标志物，且在严重缺血症状期间会短暂升高。

CC chemokine ligand-5 (CCL5/RANTES) and CC chemokine ligand-18 (CCL18/PARC) are specific markers of refractory unstable angina pectoris and are transiently raised during severe ischemic symptoms.

作者信息

Kraaijeveld A O, de Jager S C A, de Jager W J, Prakken B J, McColl S R, Haspels I, Putter H, van Berkel T J C, Nagelkerken L, Jukema J W, Biessen E A L

机构信息

Department of Cardiology and Einthoven Laboratory of Experimental Vascular Medicine C5-P, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.

出版信息

Circulation. 2007 Oct 23;116(17):1931-41. doi: 10.1161/CIRCULATIONAHA.107.706986. Epub 2007 Oct 1.

DOI:10.1161/CIRCULATIONAHA.107.706986

PMID:17909104

Abstract

BACKGROUND

Chemokines play an important role in atherogenesis and in ischemic injury and repair; however, prospective data on individual chemokines in unstable angina pectoris (UAP) are scarce. Therefore, we assessed chemokine patterns in a prospective cohort of patients with UAP.

METHODS AND RESULTS

Plasma samples of 54 patients with Braunwald class IIIB UAP were examined at baseline for 11 chemokines and 5 inflammatory mediators via multiplex analysis. Levels of CC chemokine ligand (CCL)-5 (also known as RANTES [regulated on activation, normally T-cell expressed, and secreted]; 32.7 versus 23.1 ng/mL, P=0.018) and CCL18 (also known as PARC [pulmonary and activation-regulated chemokine]; 104.4 versus 53.7 ng/mL, P=0.011) were significantly elevated in patients with refractory ischemic symptoms versus stabilized patients. Temporal monitoring by ELISA of CCL5, CCL18, and soluble CD40 ligand (sCD40) levels revealed a drop in CCL5 and sCD40L levels in all UAP patients from day 2 onward (CCL5 12.1 ng/mL, P<0.001; sCD40L 1.35 ng/mL, P<0.05), whereas elevated CCL18 levels were sustained for at least 2 days, then were decreased at 180 days after inclusion (34.5 ng/mL, P<0.001). Peripheral blood mononuclear cells showed increased protein expression of chemokine receptors CCR3 and CCR5 in CD3+ and CD14+ cells at baseline compared with 180 days after inclusion, whereas mRNA levels were downregulated, which was attributable in part to a postischemic release of human neutrophil peptide-3-positive neutrophils and in part to negative feedback. Finally, elevated CCL5 and CCL18 levels predicted future cardiovascular adverse events, whereas C-reactive protein and sCD40L levels did not.

CONCLUSIONS

We are the first to report that CCL18 and CCL5 are transiently raised during episodes of UAP, and peak levels of both chemokines are indicative of refractory symptoms. Because levels of both chemokines, as well as of cognate receptor expression by circulating peripheral blood mononuclear cells, are increased during cardiac ischemia, this may point to an involvement of CCL5/CCL18 in the pathophysiology of UAP and/or post-UAP responses.

摘要

背景

趋化因子在动脉粥样硬化形成、缺血性损伤及修复过程中发挥重要作用；然而，关于不稳定型心绞痛（UAP）中单个趋化因子的前瞻性数据却很匮乏。因此，我们在一个UAP患者的前瞻性队列中评估了趋化因子模式。

方法与结果

通过多重分析，对54例Braunwald IIIB级UAP患者的血浆样本在基线时检测了11种趋化因子和5种炎症介质。与病情稳定的患者相比，难治性缺血症状患者的CC趋化因子配体（CCL）-5（也称为调节激活正常T细胞表达和分泌的因子[RANTES]；32.7对23.1 ng/mL，P = 0.018）和CCL18（也称为肺和激活调节趋化因子[PARC]；104.4对53.7 ng/mL，P = 0.011）水平显著升高。通过酶联免疫吸附测定（ELISA）对CCL5、CCL18和可溶性CD40配体（sCD40）水平进行时间监测显示，从第2天起，所有UAP患者的CCL5和sCD40L水平均下降（CCL5为12.1 ng/mL，P<0.001；sCD40L为1.35 ng/mL，P<0.05），而CCL18水平至少持续2天升高，然后在纳入后180天时下降（34.5 ng/mL，P<0.001）。与纳入后180天时相比，外周血单个核细胞在基线时CD3+和CD14+细胞中趋化因子受体CCR3和CCR5的蛋白表达增加，而mRNA水平下调，这部分归因于缺血后人类中性粒细胞肽-3阳性中性粒细胞的释放，部分归因于负反馈。最后，升高的CCL5和CCL18水平可预测未来心血管不良事件，而C反应蛋白和sCD40L水平则不能。