冠状动脉粥样硬化性心脏病患者外周血单核细胞亚群CX3CR1表达的变化及意义

doi:10.3969/j.issn.1674-8115.2021.03.007

摘要/Abstract

摘要：

目的·探讨不同类型冠状动脉粥样硬化性心脏病（冠心病）患者外周血单核细胞亚群趋化因子受体CCR2（C-C motif chemokine receptors 2）和CX3CR1（C-X3-C motif chemokine receptor 1）表达水平的变化及其临床意义。方法·选择2014年1—6月于上海交通大学医学院附属第九人民医院住院并行冠状动脉造影（coronary angiography，CAG）的冠心病患者63例，其中急性冠脉综合征（acute coronary syndrome，ACS）患者46例（ACS组）、稳定型心绞痛（stable angina pectoris，SAP）患者17例（SAP组）。收集患者的一般资料、临床资料及检测指标。入院24 h内，抽取2组患者静脉血。采用流式细胞术检测外周血单核细胞亚群趋化因子受体CCR2和CX3CR1的表达，并据此进行细胞亚群分类。采用酶联免疫吸附试验（enzyme linked immunosorbent assay，ELISA）检测血清趋化因子CCL2（C-C motif chemokine ligand 2）和CX3CL1（C-X3-C motif chemokine ligand 1）水平，并随访患者5年内主要不良心脏事件（major adverse cardiac event，MACE）的发生情况。结果·与SAP组相比，ACS组患者单核细胞CCR2⁺CX3CR1⁺和CCR2^-CX3CR1⁺亚群比例、血清CCL2和CX3CL1的水平均较高（均P<0.05）。随访5年中，ACS组和SAP组分别有14例、1例患者发生MACE。多因素Logistic回归分析显示，超敏C反应蛋白水平、CCR2⁺CX3CR1^-和CCR2^-CX3CR1⁺亚群比例均为患者5年MACE发生的独立危险因素（均P<0.05）。结论·不同类型冠心病患者的单核细胞亚群趋化因子及其受体水平均呈特征性变化，单核细胞亚群的CX3CR1表达情况与冠心病患者远期预后相关。

关键词: 冠状动脉粥样硬化性心脏病, 冠状动脉造影, 主要不良心脏事件, 趋化因子受体

Abstract:

Objective·To investigate the expression and clinical significance of C-C motif chemokine receptor 2 (CCR2) and C-X3-C motif chemokine receptor 1 (CX3CR1) in peripheral blood monocytes subsets in patients with different types of coronary atherosclerotic heart disease (CHD).

Methods·A total of 63 CHD patients who underwent coronary angiography (CAG) in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January to June 2014 were selected, including 46 patients with acute coronary syndrome (ACS) and 17 patients with stable angina pectoris (SAP). The general data, clinical data and test indexes were collected. Within 24 h after admission, venous blood of the two groups were collected. The expression of CCR2 and CX3CR1 in peripheral blood monocyte subsets was detected by flow cytometry, and monocyte subsets were classified. Serum level of CCL2 (C-C motif chemokine ligand 2) and CX3CL1 (C-X3-C motif chemokine ligand 1) were detected by enzyme-linked immunosorbent assay (ELISA). These patients were followed up for 5 years, and the major adverse cardiac events (MACEs) were recorded.

Results·Compared with the SAP group, the proportion of CCR2⁺CX3CR1⁺ and CCR2^-CX3CR1⁺monocyte subsets, and the serum levels of CCL2 and CX3CL1 in the ACS group were higher all P<0.05). During the 5-year follow-up, 14 cases in the ACS group and 1 case in the SAP group had MACEs, respectively. Multivariate Logistic regression analysis showed that hypersensitive C-reactive protein level and the proportion of CCR2⁺CX3CR1^-and CCR2^-CX3CR1⁺monocyte subsets were independent risk factors for the occurrence of MACE in 5 years (all P<0.05).

Conclusions·Chemokine receptors and chemokines in monocyte subsets alter in different types of CHD. The expression of CX3CR1 of monocyte subsets is possibly related to the long-term outcome of CHD.

Key words: coronary atherosclerotic heart disease (CHD), coronary angiography (CAG), major adverse cardiac event (MACE), chemokine receptor

中图分类号:

R541.4

赵倩, 高霖, 王长谦, 张俊峰, 张绘莉, 卓杨. 冠状动脉粥样硬化性心脏病患者外周血单核细胞亚群CX3CR1表达的变化及意义[J]. 上海交通大学学报(医学版), 2021, 41(3): 328-333.

Qian ZHAO, Lin GAO, Chang-qian WANG, Jun-feng ZHANG, Hui-li ZHANG, Yang ZHUO. Changes and significance of CX3CR1 expression in peripheral blood monocyte subsets in patients with coronary atherosclerotic heart disease[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(3): 328-333.

图/表 4

参考文献 9

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Item	ACS group (N=46)			SAP group (N=17)	P value^⑥
Item	STEMI (N=12)	NSTEMI (N=15)	UA (N=19)	SAP group (N=17)	P value^⑥
General data
Age/year	71.92±5.14	70.37±7.94	72.11±8.97	73.00±8.10	0.228
Male/n (%)	9 (75.0)	11 (73.3)	13 (68.4)	11 (64.7)	0.348
BMI/(kg·m^-2)	25.85±1.36	25.92±2.15	25.52±1.38	25.47±1.99	0.601
Clinical data
Family history of CHD/n (%)	4 (33.3)	4 (26.7)	3 (15.8)	3 (17.6)	0.767
Smoking history/n (%)	7 (58.3)	10 (66.7)	13 (68.4)	8 (47.1)	0.095
Combined hypertension/n (%)	8 (66.7)	9 (60.0)	10 (52.6)	6 (35.3)	0.221
Combined diabetes/n (%)	4 (33.3)	5 (33.3)	9 (47.4)	6 (35.3)	0.972
Anti-platelet drugs/n (%)	12 (100.0)	15 (100.0)	19 (100.0)	17 (100.0)	-
Statins/n (%)	12 (100.0)	15 (100.0)	19 (100.0)	12 (70.6)	0.000
ACEI/ARB/n (%)	8 (66.7)	9 (60.0)	10 (52.6)	7 (41.2)	0.233
β-blocker/n (%)	7 (58.3)	7 (46.7)	8 (42.1)	6 (35.3)	0.639
Gensini score	41.75±17.97	28.40±10.06^①	23.89±7.91^③	16.59±9.64	0.000
Testing indexes
cTnI (pg·mL^-1)	44.41±38.87	18.53±22.81^②	0.07±0.07^③④	0.02±0.01	0.000
CK-MB/(U·L^-1)	577.17±449.76	172.53±108.87^③	14.11±6.38^③⑤	13.35±7.23	0.000
TC/(mmol·L^-1)	4.06±1.09	4.09±0.98	4.46±1.26	4.61±1.12	0.456
LDL-Ch/(mmol·L^-1)	2.49±1.13	2.64±1.16	2.83±1.11	2.86±1.03	0.812
HDL-Ch/(mmol·L^-1)	1.07±0.31	1.08±0.35	1.14±0.44	1.09±0.34	0.993
TAG/(mmol·L^-1)	2.28±0.54	1.51±0.72	1.95±0.84	1.82±0.96	0.940
Creatinine/(μmol·L^-1)	106.25±38.26	107.33±30.02	111.16±44.13	93.24±20.74	0.218
Fasting blood glucose /(mmol·L^-1)	6.29±2.56	6.69±2.52	6.79±2.07	6.16±2.29	0.656
Homocysteine/(μmol·L^-1)	22.14±7.90	23.47±11.20	19.44±8.03	21.14±12.29	0.437
SBP/mmHg	128.00±18.16	125.27±18.63	127.11±21.39	132.47±19.84	0.519
DBP/mmHg	71.08±8.82	72.27±12.29	74.05±15.01	78.72±15.23	0.215

Item	ACS group (N=46)			SAP group (N=17)	P value^⑥
Item	STEMI (N=12)	NSTEMI (N=15)	UA (N=19)	SAP group (N=17)	P value^⑥
General data
Age/year	71.92±5.14	70.37±7.94	72.11±8.97	73.00±8.10	0.228
Male/n (%)	9 (75.0)	11 (73.3)	13 (68.4)	11 (64.7)	0.348
BMI/(kg·m^-2)	25.85±1.36	25.92±2.15	25.52±1.38	25.47±1.99	0.601
Clinical data
Family history of CHD/n (%)	4 (33.3)	4 (26.7)	3 (15.8)	3 (17.6)	0.767
Smoking history/n (%)	7 (58.3)	10 (66.7)	13 (68.4)	8 (47.1)	0.095
Combined hypertension/n (%)	8 (66.7)	9 (60.0)	10 (52.6)	6 (35.3)	0.221
Combined diabetes/n (%)	4 (33.3)	5 (33.3)	9 (47.4)	6 (35.3)	0.972
Anti-platelet drugs/n (%)	12 (100.0)	15 (100.0)	19 (100.0)	17 (100.0)	-
Statins/n (%)	12 (100.0)	15 (100.0)	19 (100.0)	12 (70.6)	0.000
ACEI/ARB/n (%)	8 (66.7)	9 (60.0)	10 (52.6)	7 (41.2)	0.233
β-blocker/n (%)	7 (58.3)	7 (46.7)	8 (42.1)	6 (35.3)	0.639
Gensini score	41.75±17.97	28.40±10.06^①	23.89±7.91^③	16.59±9.64	0.000
Testing indexes
cTnI (pg·mL^-1)	44.41±38.87	18.53±22.81^②	0.07±0.07^③④	0.02±0.01	0.000
CK-MB/(U·L^-1)	577.17±449.76	172.53±108.87^③	14.11±6.38^③⑤	13.35±7.23	0.000
TC/(mmol·L^-1)	4.06±1.09	4.09±0.98	4.46±1.26	4.61±1.12	0.456
LDL-Ch/(mmol·L^-1)	2.49±1.13	2.64±1.16	2.83±1.11	2.86±1.03	0.812
HDL-Ch/(mmol·L^-1)	1.07±0.31	1.08±0.35	1.14±0.44	1.09±0.34	0.993
TAG/(mmol·L^-1)	2.28±0.54	1.51±0.72	1.95±0.84	1.82±0.96	0.940
Creatinine/(μmol·L^-1)	106.25±38.26	107.33±30.02	111.16±44.13	93.24±20.74	0.218
Fasting blood glucose /(mmol·L^-1)	6.29±2.56	6.69±2.52	6.79±2.07	6.16±2.29	0.656
Homocysteine/(μmol·L^-1)	22.14±7.90	23.47±11.20	19.44±8.03	21.14±12.29	0.437
SBP/mmHg	128.00±18.16	125.27±18.63	127.11±21.39	132.47±19.84	0.519
DBP/mmHg	71.08±8.82	72.27±12.29	74.05±15.01	78.72±15.23	0.215

Index	ACS group (N=46)			SAP group (N=17)	P value^④
Index	STEMI (N=12)	NSTEMI (N=15)	UA (N=19)	SAP group (N=17)	P value^④
Total WBC count/(×10⁹·L^-1)	12.76±1.92	10.99±1.91^①	8.20±2.50^②	6.56±2.17	0.000
Neutrophil count/(×10⁹·L^-1)	10.06±1.33	8.48±1.43	6.13±1.94	4.73±1.71	0.000
Lymphocyte count/(×10⁹·L^-1)	1.79±0.84	1.92±0.85	1.55±0.51	1.40±0.55	0.209
Monocyte count/(×10⁹·L^-1)	0.76±0.36	0.62±0.22	0.47±0.27^③	0.36±0.14	0.007
CX3CL1/(pg·mL^-1)	0.47±0.23	0.42±0.21	0.34±0.18	0.16±0.14	0.000
CCL2/(pg·mL^-1)	46.87±38.74	43.24±23.79	32.15±14.08	29.24±14.54	0.004
hs-CRP/(mg·dL^-1)	28.71±12.73	17.85±7.00^①	8.40±4.46^②	3.39±3.36	0.000

Index	ACS group (N=46)			SAP group (N=17)	P value^④
Index	STEMI (N=12)	NSTEMI (N=15)	UA (N=19)	SAP group (N=17)	P value^④
Total WBC count/(×10⁹·L^-1)	12.76±1.92	10.99±1.91^①	8.20±2.50^②	6.56±2.17	0.000
Neutrophil count/(×10⁹·L^-1)	10.06±1.33	8.48±1.43	6.13±1.94	4.73±1.71	0.000
Lymphocyte count/(×10⁹·L^-1)	1.79±0.84	1.92±0.85	1.55±0.51	1.40±0.55	0.209
Monocyte count/(×10⁹·L^-1)	0.76±0.36	0.62±0.22	0.47±0.27^③	0.36±0.14	0.007
CX3CL1/(pg·mL^-1)	0.47±0.23	0.42±0.21	0.34±0.18	0.16±0.14	0.000
CCL2/(pg·mL^-1)	46.87±38.74	43.24±23.79	32.15±14.08	29.24±14.54	0.004
hs-CRP/(mg·dL^-1)	28.71±12.73	17.85±7.00^①	8.40±4.46^②	3.39±3.36	0.000

Monocyte subset	ACS group (N=46)			SAP group (N=17)	P value^①
Monocyte subset	STEMI (N=12)	NSTEMI (N=15)	UA (N=19)	SAP group (N=17)	P value^①
CCR2⁺CX3CR1^-/%	5.00 (2.80, 15.78)	11.80 (8.50, 35.60)	10.20 (7.60, 14.20)	73.20 (63.90, 89.05)	0.000
CCR2⁺CX3CR1⁺/%	70.40 (57.68, 76.31)	64.50 (51.43, 70.60)	60.30 (55.90, 73.40)	5.67 (3.45, 13.45)	0.000
CCR2^-CX3CR1⁺/%	20.05 (15.41, 23.14)	17.87 (15.60, 21.90)	17.50 (10.20, 20.50)	10.50 (2.98, 13.48)	0.000