急性心肌梗死患者外周血单个核细胞miR-132、单核细胞趋化蛋白-1的表达及与预后的关系Expression of miR-132 and monocyte chemoattractant protein-1 in peripheral blood mononuclear cells of patients with acute myocardial infarction and their relationship with prognosis
李晶瑾,翟阳,靳刚,陈茜,黄欣
LI Jingjin,ZHAI Yang,JIN Gang,CHEN Qian,HUANG Xin
摘要(Abstract):
目的探讨急性心肌梗死(AMI)患者外周血单个核细胞(PBMC) miR-132、单核细胞趋化蛋白-1(MCP-1)的表达与左心室重构及预后的关系。方法 84例AMI患者作为AMI组、90例非冠心病(NCHD)患者作为NCHD组,AMI组患者根据预后再分为AMI预后不良亚组和预后良好亚组;比较2组患者入院时的临床生化指标[白细胞计数(WBC)、淋巴细胞计数(LYM)、肌酸激酶(CK)、肌酸激酶同工酶(CKMB)、高敏肌钙蛋白T(hs-cTnT)、N-末端脑钠肽前体(NT-proBNP)、甘油三酯(TG)、总胆固醇(CHOL)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]和1年随访时左心室重构及左心功能指标[左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、左室射血分数(LVEF)、左室短轴缩短率(LVFS)及心输出量(CO)],采用密度梯度离心法分离PBMC,通过RT-qPCR检测miR-132和MCP-1的表达,采用Pearson相关分析miR-132与MCP-1的相关性、AMI患者miR-132和MCP-1与心肌损伤标志物、NT-proBNP、左心室重构及功能的相关性;采用受试者工作特征曲线(ROC)分析miR-132和MCP-1对AMI及预后的诊断价值。结果 AMI组miR-132、MCP-1、WBC、LYM、CK、CKMB、hs-cTnT、NT-proBNP、TG、CHOL、LDL-C、LVESD、LVEDD均明显高于NCHD组(P<0.01);HDL-C、LVEF、LVFS、CO明显低于NCHD对照组(P<0.01);AMI组MCP-1的表达与miR-132呈正相关(r=0.71,P<0.01), miR-132和MCP-1表达与CK、CKMB、hs-cTnT、NT-proBNP、LVESD、LVEDD呈正相关(P<0.01),与LVEF、LVFS、CO呈负相关(P<0.01);AMI预后不良亚组miR-132、MCP-1、hs-cTnT、NT-proBNP、LVESD、LVEDD明显高于预后良好亚组(P<0.01),LVEF、LVFS、CO明显低于预后良好亚组(P<0.01);miR-132、MCP-1、NT-proBNP、LVESD、LVEDD、LVEF、LVFS为AMI预后的独立危险因素(P<0.05);miR-132、MCP-1预测AMI患者预后不良的曲线下面积(AUC)分别为0.84、0.74,二者联合的AUC为0.85。结论 miR-132及MCP-1在AMI患者PBMC中表达升高,与心肌损伤的程度、左室重构及左心功能相关,两者对AMI均有较好的诊断价值,有助于判断AMI患者预后。
Objective To investigate the association of the expression miR-132 and monocyte chemoattractant protein-1( MCP-1) in peripheral blood mononuclear cells( PBMCs) with left ventricular remodeling and prognosis in patients with acute myocardial infarction(AMI).Methods A total of 84 patients with AMI were taken as AMI group and 90 patients with non-coronary heart disease(NCHD) as NCHD group. The patients in AMI group were further divided into a subgroup with poor prognosis and a subgroup with good prognosis according to the prognosis. Clinical biochemistry indexes of two groups at admission was compared, including white blood cell count(WBC), lymphocyte count(LYM), creatine kinase(CK), creatine kinase isoenzyme(CKMB), high-sensitivity troponin T(hs-cTnT), N-terminal pro-brain natriuretic peptide(NT-proBNP), triglycerides(TG), total cholesterol(CHOL), high-density lipoprotein cholesterol( HDL-C), low-density lipoprotein cholesterol( LDLC), left ventricular remodeling, and left ventricular function indicators at the 1-year follow-up.Detected left ventricular function indicators included left ventricular end systolic diameter(LVESD),left ventricular end-diastolic diameter( LVEDD), left ventricular ejection fraction( LVEF), left ventricular short axis shortening rate( LVFS),and cardiac output( CO). PBMCs were isolated by density gradient centrifugation. Expression levels of miR-132 and MCP-1 were detected by RT-qPCR.Pearson correlation was used to analyze the association of miR-132 with MCP-1 and the association of miR-132 and MCP-1 with myocardial injury markers, NT-proBNP, left ventricular remodeling and functions. Receiver operating characteristic curve(ROC) was used to analyze the diagnostic values of miR-132 and MCP-1 for AMI and prognostic values.Results miR-132, MCP-1, WBC, LYM, CK,CKMB, hs-cTnT, NT-proBNP, TG, CHOL, LDL-C, LVESD, LVEDD in AMI group were significantly higher than those in NCHD group(P< 0. 01), while HDL-C, LVEF, LVFS, and CO in AMI group were significantly lower than those in NCHD group(P< 0. 01). MCP-1 expression in AMI group was positively correlated with miR-132(r= 0. 71,P< 0. 01). The expression levels of miR-132 and MCP-1 were positively correlated with CK, CKMB, hs-cTnT, NT-proBNP, LVESD, and LVEDD(P< 0. 01), negatively correlated with LVEF, LVFS, and CO(P< 0. 01). miR-132, MCP-1, hs-cTnT, NT-proBNP, LVESD, and LVEDD in the subgroup with poor prognosis of AMI were significantly higher than those in the subgroup with good prognosis(P< 0. 01), while LVEF, LVFS,and CO were significantly lower than the subgroup with good prognosis(P< 0. 01). miR-132,MCP-1, NT-proBNP, LVESD, LVEDD, LVEF, and LVFS were independent risk factors for AMI prognosis(P< 0. 05). The area under the curve(AUC) of miR-132 or MCP-1 in predicting poor prognosis of the patients with AMI was 0. 84 and 0. 74, respectively, and theAUCof the combination of miR-132 or MCP-1 was 0. 85.Conclusion The expression levels of miR-132 and MCP-1 in PBMCs of AMI patients are elevated, which are related to the degree of myocardial injury, left ventricular remodeling and left heart functions. Both miR-132 and MCP-1 have good diagnostic values in diagnosing AMI and predicting the prognosis of patients with AMI.
关键词(KeyWords):
急性心肌梗死;外周血单个核细胞;miR-132;单核细胞趋化蛋白-1;心室重构
acute myocardial infarction(AMI);peripheral blood mononuclear cells(PBMC);miR-132;monocyte chemoattractant protein-1(MCP-1);ventricular remodeling
基金项目(Foundation): 陕西省2019年重点研发计划(2019SF-164)
作者(Author):
李晶瑾,翟阳,靳刚,陈茜,黄欣
LI Jingjin,ZHAI Yang,JIN Gang,CHEN Qian,HUANG Xin
DOI: 10.19367/j.cnki.2096-8388.2022.01.018
参考文献(References):
- [1] GEOVANINI G R, LIBBY P. Atherosclerosis and inflammation:overview and updates[J]. Clin Sci(Lond),2018, 132(12):1243-1252.
- [2] FEINBERG M W, MOORE K J. microRNA regulation of atherosclerosis[J]. Circ Res, 2016, 118(4):703-720.
- [3] SINGH A, PATRO P S, AGGARWAL A. MicroRNA-132, miR-146a, and miR-155 as potential biomarkers of methotrexate response in patients with rheumatoid arthritis[J]. Clinical Rheumatology, 2019, 38(3):877-884.
- [4] PAULEY K M, SATOH M, CHAN A L, et al. Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients[J]. Arthritis Res Ther, 2008, 10(4):101.
- [5] STRUM J C, JOHNSON J H, WARD J, et al. MicroRNA132 regulates nutritional stress-induced chemokine production through repression of SirT1[J]. Mol Endocrinol,2009, 23(11):1876-1884.
- [6] QAZI T J, LU J, DURU L, et al. Upregulation of mir-132induces dopaminergic neuronal death via activating SIRT1/P53 pathway[J]. Neurosci Lett, 2021, 740:135465.
- [7] DOULAMIS I P, TZANI A I, KONSTANTOPOULOS P S, et al. A sirtuin 1/MMP2 prognostic index for myocardial infarction in patients with advanced coronary artery disease[J]. Int J Cardiol, 2017, 230:447-453.
- [8]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.急性ST段抬高型心肌梗死诊断和治疗指南(2019)[J].中华心血管病杂志,2019, 47(10):766-783.
- [9] COLLET J P, THIELE H, BARBATO E, et al. 2020ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation[J]. Eur Heart J, 2021, 42(14):1289-1367.
- [10] TAO J, XIA L, CAI Z, et al. Interaction between microRNA and DNA methylation in atherosclerosis[J].DNA Cell Biol, 2021, 40(1):101-115.
- [11]JU′ZWIK C A, DRAKE S S, ZHANG Y, et al. microRNA dysregulation in neurodegenerative diseases:a systematic review[J]. Prog Neurobiol, 2019, 182:101664.
- [12]ZHAO L Z, JIAO J C, PENG W, et al. OxLDL induces vascular endothelial cell pyroptosis through miR-125a-5p/TET2 pathway[J]. Journal of Cellular Physiology,2019, 234(5):7475-7491.
- [13]RAITOHARJU E, OKSALA N, LEHTIM?KI T. MicroRNAs in the atherosclerotic plaque[J]. Clin Chem, 2013,59(12):1708-1721.
- [14]LI D, YANG P, XIONG Q, et al. MicroRNA-125a/b-5p inhibits endothelin-1 expression in vascular endothelial cells[J]. J Hypertens, 2010, 28(8):1646-1654.
- [15]YAO Y, LI Q, WANG W, et al. Glucagon-like peptide-1 modulates cholesterol homeostasis by suppressing the miR-19b-induced downregulation of ABCA1[J]. Cell Physiol Biochem, 2018, 50(2):679-693.
- [16]CHOE N, KWON J S, KIM J R, et al. The microRNA miR-132 targets lrrfip1 to block vascular smooth muscle cell proliferation and neointimal hyperplasia[J]. Atherosclerosis, 2013, 229(2):348-355.
- [17]LIU X, YOU L, ZHOU R, et al. Significant association between functional microRNA polymorphisms and coronary heart disease susceptibility:a comprehensive metaanalysis involving 16484 subjects[J]. Oncotarget, 2017,8(4):5692-5702.
- [18]NAHID M A, YAO B, DOMINGUEZGUTIERREZ P R,et al. Regulation of TLR2-mediated tolerance and crosstolerance through IRAK4 modulation by miR-132 and miR-212[J]. J Immunol, 2013, 190(3):1250-1263.
- [19]LI D, WANG A, LIU X, et al. microRNA-132 enhances transition from inflammation to proliferation during wound healing[J]. J Clin Invest, 2015, 125(8):3008-3026.
- [20]WANG W, LI X, REN L, et al. miR-132 relieves vascular endothelial inflammation and improves endothelial function in atherosclerosis rats by regulating SIRT1[J].Minerva Endocrinol, 2020, 45(2):158-161.
- [21] STYPINSKA B, WAJDA A, WALCZUK E, et al. The serum cell-free microRNA expression profile in MCTD,SLE, SSc, and RA Patients[J]. J Clin Med, 2020, 9(1):161.
- [22]苏显都,林明利,符步远,等.类风湿关节炎患者外周血单核细胞miR-24、miR-132表达及临床意义[J].中国免疫学杂志,2020, 36(1):90-93.
- [23]TABAS I, LICHTMAN A H. Monocyte-macrophages and T cells in atherosclerosis[J]. Immunity, 2017, 47(4):621-634.
- [24]ZAHRA S, ZIBA N S F, MILAD B, et al. Dysregulated expression of STAT1, miR-150, and miR-223 in peripheral blood mononuclear cells of coronary artery disease patients with significant or insignificant stenosis[J].Journal of Cellular Biochemistry, 2019, 120(12):19810-19824.
- [25] MAHLER S A, REGISTER T C, RILEY R F, et al.Monocyte chemoattractant protein-1 as a predictor of coronary atherosclerosis in patients receiving coronary angiography[J]. Crit Pathw Cardiol, 2018, 17(2):105-110.
文章评论(Comment):
|
||||||||||||||||||
|
||||||||||||||||||