Atherosclerosis 238 (2015) 365e369
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Serum chemokine CCL17/thymus activation and regulated chemokine is correlated with coronary artery diseases Yicong Ye 1, Xinglin Yang 1, Xiliang Zhao 1, Lianfeng Chen 1, Hongzhi Xie, Yong Zeng, Zhujun Shen, Zhongjie Fan, Zhenyu Liu, Shuyang Zhang* Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 November 2014 Received in revised form 16 December 2014 Accepted 20 December 2014 Available online 23 December 2014
Objective: It was recently reported that chemokine CC-motif ligand 17 (CCL17)-expressing dendritic cells drove atherosclerosis by restraining regulatory T cell homeostasis in an animal model. Our preliminary study has shown that serum CCL17 levels may be associated with coronary artery disease (CAD). The aim of this study was to confirm the relationship between serum CCL17 levels and CAD. Methods: Patients presenting to our center for coronary angiography between January 2013 and December 2013 were recruited for the study. Serum CCL17 levels were determined by enzyme-linked immunosorbent assay. Atherosclerosis severity was assessed in each patient according to the Gensini score. Results: In total, 971 consecutive patients were enrolled in this study, including 158 non-CAD patients and 813 CAD patients (238 with stable angina pectoris, 321 with unstable angina, 128 with non-ST elevation myocardial infarction, and 126 with ST elevation myocardial infarction). CAD patients had higher serum CCL17 levels compared to patients without CAD [265.90 (170.80e376.65) pg/mL versus 218.35 (142.83e293.45) pg/ mL, p < 0.001]. After adjusting for traditional risk factors, serum CCL17 levels remained associated with CAD. Meanwhile, there was a significant linear trend between serum CCL17 levels and the different CAD subtypes (p for linear trend ¼ 0.002). Finally, serum CCL17 levels (per 100 pg/mL) were positively associated with the Gensini score (B 2.310; 95% CI 0.503e4.118; p ¼ 0.012) even after adjusting for confounding factors. Conclusion: Serum CCL17 levels are associated with CAD and atherosclerosis severity independently of traditional cardiovascular risk factors. © 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Chemokine CC-motif ligand 17 Thymus activation and regulated chemokine Coronary artery disease Atherosclerosis
1. Introduction Atherosclerosis is an inflammatory process that promotes atheroma development and progression [1,2]. Chemokines are a family of small chemotactic cytokines, and they have now been recognized as important contributors to the atherosclerosis and cardiovascular disease [3]. Several types of chemokines are expressed within atherosclerotic lesions in a region- and stagespecific manner [4], and circulating chemokines have been considered as important markers for atherosclerosis. Monocyte chemoattractant protein-1 is the first prototypic CC-motif
* Corresponding author. E-mail address: [email protected] (S. Zhang). 1 Yicong Ye, Xinglin Yang, Xiliang Zhao, and Lianfeng Chen contributed equally to the study. http://dx.doi.org/10.1016/j.atherosclerosis.2014.12.047 0021-9150/© 2014 Elsevier Ireland Ltd. All rights reserved.
chemokine, and its serum levels were increased in many atherosclerotic patients, including those suffering from ischemic stroke, myocardial infarction and peripheral artery disease [5,6]. Chemokine (C-X-C motif) ligand 16 is a recently discovered2 T-cell chemoattractant and oxidized low-density lipoprotein scavenger receptor [7,8], and its circulating concentration was also altered in coronary artery disease (CAD) patients [9]. Weber et al. [10] recently found that chemokine CC ligand 17 (CCL17, also known as thymus activation and regulated chemokine) is an important atherosclerosis regulator, as it inhibits regulatory T cell retention. Our previous study showed that CAD patients had significantly higher serum CCL17 levels compared to non-CAD patients and serum CCL17 levels were independently associated with CAD [11]. However, due to the small sample size, the association required further confirmation in a large-scale study.
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Y. Ye et al. / Atherosclerosis 238 (2015) 365e369
The aim of this study was to confirm the relationship between serum CCL17 levels and CAD. Furthermore, we tried to determine the association between serum CCL17 levels and various CAD subtypes and severities. 2. Materials and methods 2.1. Study population Patients presenting to Peking Union Medical College Hospital for coronary angiography between January 2013 and December 2013 were recruited consecutively into the study. Subjects with 20 min) anginal pain at rest, new onset angina (Class II or III according to the Classification of the Canadian Cardiovascular Society), recent destabilization of previously stable angina with at least Canadian Cardiovascular Society Class III angina characteristics (crescendo angina), or post-myocardial infarction angina [12]. SAP was defined as angina that did not fulfill the above UA criteria [13]. Myocardial infarction was defined as a rise and/or fall of cardiac troponin with at least one value above the 99th percentile upper reference limit and with at least one of the following: (1) ischemia symptoms, (2) new or presumed new significant STsegmenteT wave (STeT) changes or new left bundle branch block (LBBB), (3) development of pathological Q waves in the ECG (4) imaging evidence of new viable myocardium loss or new regional wall motion abnormality, (5) identification of an intracoronary thrombus by angiography or autopsy. Patients with myocardial infarction were further divided into STEMI and NSTEMI according to their ECG patterns [14]. Non-CAD patients were sub-divided into a normal coronary artery group (
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Serum chemokine CCL17/thymus activation and regulated chemokine is correlated with coronary artery diseases Yicong Ye 1, Xinglin Yang 1, Xiliang Zhao 1, Lianfeng Chen 1, Hongzhi Xie, Yong Zeng, Zhujun Shen, Zhongjie Fan, Zhenyu Liu, Shuyang Zhang* Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 November 2014 Received in revised form 16 December 2014 Accepted 20 December 2014 Available online 23 December 2014
Objective: It was recently reported that chemokine CC-motif ligand 17 (CCL17)-expressing dendritic cells drove atherosclerosis by restraining regulatory T cell homeostasis in an animal model. Our preliminary study has shown that serum CCL17 levels may be associated with coronary artery disease (CAD). The aim of this study was to confirm the relationship between serum CCL17 levels and CAD. Methods: Patients presenting to our center for coronary angiography between January 2013 and December 2013 were recruited for the study. Serum CCL17 levels were determined by enzyme-linked immunosorbent assay. Atherosclerosis severity was assessed in each patient according to the Gensini score. Results: In total, 971 consecutive patients were enrolled in this study, including 158 non-CAD patients and 813 CAD patients (238 with stable angina pectoris, 321 with unstable angina, 128 with non-ST elevation myocardial infarction, and 126 with ST elevation myocardial infarction). CAD patients had higher serum CCL17 levels compared to patients without CAD [265.90 (170.80e376.65) pg/mL versus 218.35 (142.83e293.45) pg/ mL, p < 0.001]. After adjusting for traditional risk factors, serum CCL17 levels remained associated with CAD. Meanwhile, there was a significant linear trend between serum CCL17 levels and the different CAD subtypes (p for linear trend ¼ 0.002). Finally, serum CCL17 levels (per 100 pg/mL) were positively associated with the Gensini score (B 2.310; 95% CI 0.503e4.118; p ¼ 0.012) even after adjusting for confounding factors. Conclusion: Serum CCL17 levels are associated with CAD and atherosclerosis severity independently of traditional cardiovascular risk factors. © 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Chemokine CC-motif ligand 17 Thymus activation and regulated chemokine Coronary artery disease Atherosclerosis
1. Introduction Atherosclerosis is an inflammatory process that promotes atheroma development and progression [1,2]. Chemokines are a family of small chemotactic cytokines, and they have now been recognized as important contributors to the atherosclerosis and cardiovascular disease [3]. Several types of chemokines are expressed within atherosclerotic lesions in a region- and stagespecific manner [4], and circulating chemokines have been considered as important markers for atherosclerosis. Monocyte chemoattractant protein-1 is the first prototypic CC-motif
* Corresponding author. E-mail address: [email protected] (S. Zhang). 1 Yicong Ye, Xinglin Yang, Xiliang Zhao, and Lianfeng Chen contributed equally to the study. http://dx.doi.org/10.1016/j.atherosclerosis.2014.12.047 0021-9150/© 2014 Elsevier Ireland Ltd. All rights reserved.
chemokine, and its serum levels were increased in many atherosclerotic patients, including those suffering from ischemic stroke, myocardial infarction and peripheral artery disease [5,6]. Chemokine (C-X-C motif) ligand 16 is a recently discovered2 T-cell chemoattractant and oxidized low-density lipoprotein scavenger receptor [7,8], and its circulating concentration was also altered in coronary artery disease (CAD) patients [9]. Weber et al. [10] recently found that chemokine CC ligand 17 (CCL17, also known as thymus activation and regulated chemokine) is an important atherosclerosis regulator, as it inhibits regulatory T cell retention. Our previous study showed that CAD patients had significantly higher serum CCL17 levels compared to non-CAD patients and serum CCL17 levels were independently associated with CAD [11]. However, due to the small sample size, the association required further confirmation in a large-scale study.
366
Y. Ye et al. / Atherosclerosis 238 (2015) 365e369
The aim of this study was to confirm the relationship between serum CCL17 levels and CAD. Furthermore, we tried to determine the association between serum CCL17 levels and various CAD subtypes and severities. 2. Materials and methods 2.1. Study population Patients presenting to Peking Union Medical College Hospital for coronary angiography between January 2013 and December 2013 were recruited consecutively into the study. Subjects with 20 min) anginal pain at rest, new onset angina (Class II or III according to the Classification of the Canadian Cardiovascular Society), recent destabilization of previously stable angina with at least Canadian Cardiovascular Society Class III angina characteristics (crescendo angina), or post-myocardial infarction angina [12]. SAP was defined as angina that did not fulfill the above UA criteria [13]. Myocardial infarction was defined as a rise and/or fall of cardiac troponin with at least one value above the 99th percentile upper reference limit and with at least one of the following: (1) ischemia symptoms, (2) new or presumed new significant STsegmenteT wave (STeT) changes or new left bundle branch block (LBBB), (3) development of pathological Q waves in the ECG (4) imaging evidence of new viable myocardium loss or new regional wall motion abnormality, (5) identification of an intracoronary thrombus by angiography or autopsy. Patients with myocardial infarction were further divided into STEMI and NSTEMI according to their ECG patterns [14]. Non-CAD patients were sub-divided into a normal coronary artery group (
