de Jager Saskia C A, Kraaijeveld Adriaan O, Grauss Robert W, de Jager Wilco, Liem Su-San, van der Hoeven Bas L, Prakken Berent J, Putter Hein, van Berkel Theo J C, Atsma Douwe E, Schalij Martin J, Jukema J Wouter, Biessen Erik A L
Division of Biopharmaceutics, Leiden Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, Einsteinweg 55, PO Box 9502, 2300 RA Leiden, Leiden, The Netherlands.
J Mol Cell Cardiol. 2008 Sep;45(3):446-52. doi: 10.1016/j.yjmcc.2008.06.003. Epub 2008 Jun 21.
As chemokines are considered instrumental in thrombotic plaque rupture and erosion as well as in ischemia-reperfusion injury processes, we aimed to identify previously unknown chemokines associated with acute coronary syndromes. Plasma of 44 patients with acute myocardial infarction (AMI) and 22 controls were profiled for a panel of chemokines by multiplex analysis. Levels of CCL3 were prospectively verified in 54 patients with unstable angina pectoris (UAP). An AMI mouse model was used to assess the relationship between differentially expressed chemokines and myocardial ischemia. CCL3 levels were significantly elevated in AMI vs. controls (P=0.02) albeit, that adjustment for confounding factors attenuated this association. In support of a direct association with cardiac ischemia CCL3 levels were also seen to be elevated in patients with UAP at baseline and significantly down-regulated after 180 days (P<0.001). Importantly, baseline upper quartile levels were strongly correlated with future acute coronary syndromes (Likelihood Ratio 11.5; P<0.01). Furthermore circulating levels of CCL3 were significantly enhanced after AMI in mice (P=0.02), while CCR5(+) T-cell numbers were increased as well, suggestive of CCL3 driven T-cell homing towards the ischemic area. CCL3 levels are elevated during ACS and released upon ischemia. Since CCL3 specifically predicts future cardiovascular events, it may serve as a predictive biomarker.
由于趋化因子被认为在血栓形成性斑块破裂和糜烂以及缺血再灌注损伤过程中起重要作用，我们旨在鉴定与急性冠状动脉综合征相关的此前未知的趋化因子。通过多重分析对44例急性心肌梗死（AMI）患者和22例对照的血浆进行了一组趋化因子分析。对54例不稳定型心绞痛（UAP）患者的CCL3水平进行了前瞻性验证。使用AMI小鼠模型评估差异表达的趋化因子与心肌缺血之间的关系。与对照组相比，AMI患者的CCL3水平显著升高（P = 0.02），尽管对混杂因素进行调整后减弱了这种关联。为支持CCL3与心脏缺血的直接关联，UAP患者在基线时CCL3水平也升高，180天后显著下调（P < 0.001）。重要的是，基线四分位数上限水平与未来急性冠状动脉综合征密切相关（似然比11.5；P < 0.01）。此外，小鼠AMI后循环中的CCL3水平显著升高（P = 0.02），同时CCR5(+) T细胞数量也增加，提示CCL3驱动T细胞归巢至缺血区域。ACS期间CCL3水平升高并在缺血时释放。由于CCL3可特异性预测未来心血管事件，它可能作为一种预测性生物标志物。
