microRNA-146a与冠心病患者斑块稳定性的相关性

徐栩; 武力勇; 周明礼; 朱国富

doi:10.12259/j.issn.2095-610X.S20201119

microRNA-146a与冠心病患者斑块稳定性的相关性

doi: 10.12259/j.issn.2095-610X.S20201119

1.
昆明市第一人民医院甘美医院老年病科，云南昆明　650011
2.
昆明医科大学第二附属医院心血管内科，云南昆明　650101

基金项目: 国家自然科学基金资助项目（81820092）

详细信息

作者简介:
徐栩（1982～），女，云南昆明人，医学硕士，主治医师，主要从事冠心病研究工作

通讯作者:
朱国富，E-mail：46467528@qq.com

中图分类号: R541.6
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- 被引次数: 0
出版历程
- 收稿日期: 2020-10-12
- 网络出版日期: 2020-12-03
- 刊出日期: 2020-11-25

Relationship between microRNA-146a and the Plaque Stability in Coronary Heart Disease Patients

1.
Dept. of Geriatrics，Ganmei Hospital，Kunming First People’s Hospital，Kunming Yunnan 650011
2.
Dept. of Cardiology，The 2nd Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650101，China

摘要

摘要: 目的探讨microRNA-146a（miR-146a）与冠心病斑块稳定性的相关性。方法共收集胸痛患者324例。采用实时聚合酶链反应（Real-time PCR）检测miR-146a的表达。ELISA法检测hs-CRP、IL-6、IL-8水平。采用冠脉造影评价冠状动脉狭窄程度。应用血管内超声（IVUS）评价冠状动脉狭窄病变斑块稳定性。结果（1）UAP组和AMI组hs-CRP、IL-6、IL-8水平较CPS组明显升高（P < 0.01）；（2）冠心病患者外周血单个核细胞（PBMCs）和血浆miR-146a表达明显高于非冠心病组（P < 0.05，P < 0.001）；（3）miR-146a在SAP组、UAP组和AMI组的表达高于CPS组（P < 0.01，P < 0.001，P < 0.001），miR-146a在血浆中的表达模式与PBMCs一致；（4）易损斑块组外周血单个核细胞和血浆miR-146a的表达明显高于稳定斑块组（P < 0.05）；（5）软斑块组PBMCs和血浆miR-146a水平显著高于纤维斑块组和钙化斑块组（P < 0.05）。结论 miR-146a的表达与冠状动脉狭窄病变斑块稳定性密切相关。
- miR-146a /
- 冠心病 /
- 血管内超声 /
- 斑块稳定性
Abstract: Objectives To investigate the association between microRNA-146a（miR-146a）and the plaque stability in patients with coronary heart disease. Methods Real-time PCR was used to measure miR-146a expression in 324 patients. ELISA was used to measure the level of hs-CRP, IL-6 and IL-8. Coronary angiography was used to evaluate the degree of coronary artery stenosis. Intravascular ultrasound（IVUS）was used to evaluate the plaque stability of coronary stenotic lesions. Results （1）The levels of hs-CRP, IL-6 and IL-8 were significantly increased in the UAP and AMI groups compared with the CPS groups（P < 0.01）.（2）The miR-146a expression in peripheral blood mononuclear cells（PBMCs）and plasma was significantly higher in CAD patients than those in non-CAD group（P < 0.05, P < 0.001）.（3）The miR-146a expression in PBMCs was higher in SAP, UAP and AMI group than CPS group（P < 0.01, P < 0.001, P < 0.001）. The expression patterns of miR-146a in plasma was consistent with that of PBMCs.（4）The expression of miR-146a in PBMCs and plasma were significantly higher in vulnerable plaque group than those in stable plaque group（P < 0.05）.（5）The level of miR-146a in PBMCs and plasma was significantly higher in soft plaque group than those in fibrous plaque group and calcified plaque group（P < 0.05）. Conclusions The expression of miR-146a is associated with the plaque stability of coronary stenotic lesions.
- miR-146a /
- Coronary artery disease /
- IVUS /
- Plaque stability

HTML全文

图 1 CAD组及non-CAD组患者的miR-146a的表达水平。

A：PBMCs；B：血浆　　　　　　　　　　　　　　　　与non-CAD组比较，*P < 0.05；与non-CAD组比较，***P < 0.001。

Figure 1. The expression of miR-146a in patients with CAD and non-CAD

下载: 全尺寸图片幻灯片

图 2 四组患者miR-146a的表达水平

A：PBMCs；B：血浆。与CPS组比较，**P < 0.01；与CPS组比较，***P < 0.001；与SAP组比较，^￥P < 0.01；与UAP组比较，^#P < 0.01。

Figure 2. The expression of miR-146a in four groups.

下载: 全尺寸图片幻灯片

表 1 基础临床资料（$\bar x \pm s $）

Table 1. Basic clinical data（$\bar x \pm s $）

项目	CPS组	SAP组	UAP组	AMI组	F/χ²	P
人数	86	91	105	52
年龄	60 ± 8	62 ± 8	3 ± 7	61 ± 7	F = 2.44	0.06
性别（男/女）	35/51	45/46	52/53	26/28	χ² = 1.89	0.60
危险因素[n （%）]
高血压	39（45）	41（45）	43（41）	21（40）	χ² = 0.67	0.88
糖尿病	19（22）	34（37）	40（38）	19（37）	χ² = 6.84	0.08
高脂血症	30（35）	37（41）	45（43）	17（33）	χ² = 2.23	0.53
吸烟	29（35）	31（35）	37（38）	17（33）	χ² = 0.11	0.99
hs-CRP（mg/L）	1.16 ± 0.38	1.79 ± 0.52	2.62 ± 0.92^*	3.98 ± 0.76^*&#	F = 231.4	0.00
IL-6（ng/L）	2.30 ± 1.05	4.04 ± 0.99	8.95 ± 2.99^*&	12.48 ± 4.86^*&#	F = 234.8	0.00
IL-8（ng/L）	17.40 ± 6.24	75.23 ± 19.65^*	87.54 ± 13.12^*	108.72 ± 23.25^*&#	F = 513.9	0.00
与CPS组比较，*P < 0.01；与SAP组比较，^&P < 0.05；与UAP组比较，^#P < 0.05。

下载: 导出CSV

表 2 两组患者PBMCs及血浆中miR-146a、IL-6、Il-8及hs-CRP的水平（$\bar x \pm s $）

Table 2. Levels of miR-146a，IL-6，IL-8 and hs-CRP in PBMCs and plasma of the two groups（$\bar x \pm s $）

项目	n	PBMCs中miR-146a	血浆中miR-146a	IL-6（ng/L）	Il-8（ng/L）	hs-CRP（mg/L）
稳定斑块组	53	1.42 ± 0.36	1.11 ± 0.20	6.51 ± 2.65	72.40 ± 23.20	2.25 ± 0.95
易损斑块组	60	2.94 ± 0.78	2.04 ± 0.49	7.13 ± 2.98	80.32 ± 17.82	2.31 ± 0.90
F值		26.16	32.29	2.425	1.501	0.885
P值		0.029*	0.032*	0.545	0.058	0.663
^*P < 0.05。

下载: 导出CSV

表 3 三组患者PBMCs及血浆中miR-146a、IL-6、IL-8及hs-CRP的水平（$\bar x \pm s $）

Table 3. Levels of miR-146a，IL-6，IL-8 and hs-CRP in PBMCs and plasma of three groups（$\bar x \pm s $）

项目	n	PBMCs中miR-146a	血浆中miR-146a	IL-6（ng/L）	Il-8（ng/L）	hs-CRP（mg/L）
钙化斑块	33	1.41 ± 0.30	1.19 ± 0.18	5.78 ± 2.26	75.08 ± 24.96	2.42 ± 0.90
纤维斑块	37	2.88 ± 0.74^*	1.82 ± 0.46^*	5.98 ± 3.25	78.56 ± 22.20	2.04 ± 0.90
软斑块	43	3.40 ± 0.92^*#	2.28 ± 0.66^*#	7.82 ± 2.94	82.40 ± 14.02	2.50 ± 0.90
F		113.2	99.24	4.652	1.178	2.251
P		0.000	0.000	0.598	0.785	0.842
与钙化斑块组比较，*P < 0.05；与纤维斑块组比较，^#P < 0.05。

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参考文献(20)

[1]	胡盛寿,高润霖,刘力生,等. 《中国心血管病报告2018》概要[J].中国循环杂志,2019,34(3):209-220. doi: 10.3969/j.issn.1000-3614.2019.03.001
[2]	Geovanini G R,Libby P. Atherosclerosis and inflammation:overview and updates[J]. Clin Sci(Lond),2018,132(12):1243-1252. doi: 10.1042/CS20180306
[3]	Zhong L,Simard M J,Huot J. Endothelial microRNAs regulating the NF-κB pathway and cell adhesion molecules during inflammation[J]. FASEB J,2018,32(8):4070-4084. doi: 10.1096/fj.201701536R
[4]	Churov A,Summerhill V,Grechko A,et al. MicroRNAs as potential biomarkers in atherosclerosis[J]. Int J Mol Sci,2019,20(22):5547. doi: 10.3390/ijms20225547
[5]	Bostjancic E,Glavac D. Importance of microRNAs in skin morphogenesis and diseases[J]. Acta Dermatovenerol Alp Panonica Adriat,2008,17(3):95-102.
[6]	Stanczyk J,Pedrioli D M,Brentano F,et al. Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis[J]. Arthritis Rheum,2008,58(4):1001-1009. doi: 10.1002/art.23386
[7]	Chen X,Gao Q,Zhou L,et al. MiR-146a alleviates inflammation of acute gouty arthritis rats through TLR4/MyD88 signal transduction pathway[J]. Eur Rev Med Pharmacol Sci,2019,23(21):9230-9237.
[8]	Yao R,Ma Y,Du Y,et al. The altered expression of inflammation-related microRNAs with microRNA-155 expression correlates with Th17 differentiation in patients with acute coronary syndrome[J]. Cell Mol Immunol,2011,8(6):486-495. doi: 10.1038/cmi.2011.22
[9]	Zhu G F,Yang L X,Guo R W,et al. microRNA-155 is inversely associated with severity of coronary stenotic lesions calculated by the Gensini score[J]. Coron Artery Dis,2014,25(4):304-310. doi: 10.1097/MCA.0000000000000088
[10]	Mintz G S,Nissen S E,Anderson W D,et al. American college of cardiology clinical expert consensus document on standards for acquisition,measurement and reporting of Intravascular Ultrasound Studies(IVUS). A report of the American college of cardiology task force on clinical expert consensus documents[J]. J Am Coll Cardiol,2001,37(5):1478-1492. doi: 10.1016/S0735-1097(01)01175-5
[11]	Endo M,Hibi K,Shimizu T,et al. Impact of ultrasound attenuation and plaque rupture as detected by intravascular ultrasound on the incidence of no-reflow phenomenon after percutaneous coronary intervention in ST-segment elevation myocardial infarction[J]. J Am Coll Cardiol Intv,2010,3(5):540-549. doi: 10.1016/j.jcin.2010.01.015
[12]	Livak K J,Schmittgen T D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T))Method[J]. Methods,2001,25(4):402-408. doi: 10.1006/meth.2001.1262
[13]	Tayefi M,Tajfard M,Saffar S,et al. hs-CRP is strongly associated with coronary heart disease(CHD):A data mining approach using decision tree algorithm[J]. Comput Methods Programs Biomed,2017,141:105-109. doi: 10.1016/j.cmpb.2017.02.001
[14]	Tajfard M,Latiff L A,Rahimi H R,et al. Serum concentrations of MCP-1 and IL-6 in combination predict the presence of coronary artery disease and mortality in subjects undergoing coronary angiography[J]. Mol Cell Biochem,2017,435(1-2):37-45. doi: 10.1007/s11010-017-3054-5
[15]	Glaser R,Selzer F,Faxon D P,et al. Clinical progression of incidental,asymptomatic lesions discovered during culprit vessel coronary intervention[J]. Circulation,2005,111(2):143-149. doi: 10.1161/01.CIR.0000150335.01285.12
[16]	Taganov K D,Boldin M P,Chang K J,et al. NF-kappaB-dependent induction of microRNA miR-146,an inhibitor targeted to signaling proteins of innate immune responses[J]. Proc Natl Acad Sci USA,2006,103(33):12481-12486. doi: 10.1073/pnas.0605298103
[17]	Zeng Z,Gong H,Li Y,et al. Upregulation of miR-146a contributes to the suppression of inflammatory responses in LPS-induced acute lung injury[J]. Exp Lung Res,2013,39(7):275-282. doi: 10.3109/01902148.2013.808285
[18]	Gao M,Wang X,Zhang X,et al. Attenuation of cardiac dysfunction in polymicrobial sepsis by microRNA-146a is mediated via targeting of IRAK1 and TRAF6 expression[J]. J Immunol,2015,195(2):672-682. doi: 10.4049/jimmunol.1403155
[19]	Pundziute G,Schuijf J D,van Velzen J E,et al. Assessment with multi-slice computed tomography and gray-scale and virtual histology intravascular ultrasound of gender-specific differences in extent and composition of coronary atherosclerotic plaques in relation to age[J]. Am J Cardiol,2010,105(4):480-486. doi: 10.1016/j.amjcard.2009.09.054
[20]	Blaha M J,Nasir K,Rivera J J,et al. Gender differences in coronary plaque composition by coronary computed tomography angiography[J]. Coron Artery Dis,2009,20(8):506-512. doi: 10.1097/MCA.0b013e328331368d

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