CMTM5基因与冠心病患者支架内再狭窄发生风险

doi:10.19723/j.issn.1671-167X.2020.05.010

摘要/Abstract

摘要：

目的:探讨趋化素样因子超家族成员5 (CKLF-like marvel transmembrane domain containing member, CMTM5)基因与冠心病患者支架内再狭窄(in-stent restenosis, ISR)发生风险及该基因对人血管内皮细胞(endothelial cells, ECs)增殖和迁移作用及其机制。方法: 选择2015年1月至2016年12月在首都医科大学附属北京世纪坛医院心血管内科接受住院治疗并行经皮冠状动脉介入治疗手术的冠心病患者,共计124例,采用光学比浊法测定血小板聚集率并进行血小板高反应性分组;冠脉造影术明确患者支架内再狭窄发生;RT-PCR法测定CMTM5基因表达;构建CMTM5基因过表达、敲减及对照组内皮细胞系,采用细胞计数法、MTT法、Brdu掺入实验和流式细胞术检测ECs增殖能力,刮伤和Transwell实验检测ECs迁移能力,Western-blot检测信号通路表达。结果: CMTM5基因在血小板高反应性(high on aspirin platelet reactivity,HAPR)组表达量为非血小板高反应性(no-high on aspirin platelet reactivity,No-HAPR)组表达量的1.72倍(P<0.05)。HAPR组ISR发生率为25.8%(8例), No-HAPR组ISR发生率为 9.7%(9例), HAPR组患者ISR的发生率高于No-HAPR组的发生率(P=0.04,OR=2.95,95%CI:1.16~7.52),表明该基因与冠心病患者支架术后支架内再狭窄发生风险显著相关(P<0.05)。CMTM5基因过表达抑制ECs增殖和迁移能力(P<0.05), PI3K/Akt信号通路参与该基因对内皮细胞增殖和迁移调控作用。结论:CMTM5基因与冠心病患者支架内再狭窄事件发生风险可能存在相关性,CMTM5基因通过PI3K/Akt信号通路参与调控ECs增殖和迁移。

关键词: 趋化素样因子超家族成员5, 内皮细胞, 血小板反应性, 心血管事件

Abstract:

Objective: To elucidate the correlation between CKLF-like marvel transmembrane domain containing member (CMTM5) gene and the risk of in-stent restenosis (ISR) with coronary artery disease (CAD) patients and to detect the effects and mechanisms of CMTM5-stimulated genes on human vascular endothelial cells (ECs) proliferation and migration. Methods: A total of 124 hospitalized patients in Shijitan Hospital were enrolled in this study. All the CAD patients were detected with platelet reactivity and grouped into two groups according to platelet reactivity; ISR was conformed by coronary angiography; RT-PCR method was used to detect CMTM5 gene expression; The CMTM5 over expression, reduction and control EC lines were established; Cell count, MTT, Brdu and flow cytometry methods were used to detect the proliferation of ECs, scratch and transwell experiments to test the migration of ECs, Western blot was used to detect signal path expressions. Results: CMTM5 gene expression in HAPR (High on aspirin platelet reactivity) group was 1.72 times compared with No-HAPR group, which was significantly higher than No-HAPR group. HAPR group ISR rate was 25.8% (8 cases), the incidence of No-HAPR ISR group was 9.7% (9 cases), and the results showed that in HAPR group, the incidence of ISR was significantly higher than that in No-HAPR group (P=0.04, OR=0.04, 95%CI=1.16-7.52), which showed that CMTM5 gene was significantly correlated with the risk of ISR. In HAPR group ISR rate was 25.8% (8 cases), the incidence of ISR in No-HAPR group was 9.7% (9 cases), and the results showed that the risk of ISR in HAPR group was significantly higher than that in No-HAPR group. All the results showed that CMTM5 was significantly correlated with the risk of ISR in CAD patients (P<0.05). CMTM5 overexpression inhibited the proliferation and migration ability of ECs (P<0.05), PI3K/Akt signaling pathways were involved in the role of regulation on ECs. Conclusion: Our results revealed that CMTM5 gene was closely related with ISR, CMTM5 overexpression may repress ECs proliferation and migration through regulating PI3K-Akt signaling.

Key words: Platelet reactivity, CKLF-like marvel transmembrane dimain containing member 5, Coronary artery diseases, In-stent restenosis

中图分类号:

R543.3

刘滕飞,林涛,任利辉,李广平,彭建军. CMTM5基因与冠心病患者支架内再狭窄发生风险[J]. 北京大学学报（医学版）, 2020, 52(5): 856-862.

Teng-fei LIU,Tao LIN,Li-hui REN,Guang-ping LI,Jian-jun PENG. Association of CMTM5 gene expression with the risk of in-stent restenosis in patients with coronary artery disease after drug-eluting stent implantation and the effects and mechanisms of CMTM5 on human vascular endothelial cells[J]. Journal of Peking University (Health Sciences), 2020, 52(5): 856-862.

图/表 7

表1

HAPR组和No-HAPR组的临床基线资料"

Variables	HAPR(n=31)	No-HAPR(n=93)	P
Age/years, $x -$ ±s	76.3±7.3	74.8±8.9	0.063
Male, n(%)	27(87.1)	72(77.4)	0.308
BMI/(kg/m²), $x -$ ±s	26.1±3.3	24.5±3.1	0.451
Hypertension, n(%)	25(80.6)	66(71.0)	0.354
Diabetes, n(%)	12(38.7)	32(34.4)	0.670
Current smoking, n(%)	11(35.5)	15(16.1)	0.039^*
Hyperlipidemia, n(%)	27(87.1)	75(80.6)	0.589
Essential medicines, n(%)	14(45.2)	55(59.1)	0.212
ACEI/ARB	22(70.9)	61(65.6)	0.663
β-blocker	12(38.7)	45(48.4)	0.408
CCB	13(41.9)	31(33.3)	0.395
Nitrates	24(77.4)	81(87.1)	0.249
Stains	27(87.1)	72(77.4)	0.308
Cardiovascular events, n(%)	8 (25.8)	9 (9.7)	0.037

表1

表2

图1

图2

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图5

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Risk factors	HR	95%CI	P
ΔCt CMTM5	0.086	0.053-0.099	0.010
Current smoking	1.998	1.050-3.802	0.035