高温需求蛋白A2在急性ST段抬高型心肌梗死患者中的变化及临床意义
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摘要
目的分析急性ST段抬高型心肌梗死(STEMI)患者循环中高温需求蛋白A2(HtrA2)水平的变化及临床意义。方法纳入2017年1至12月于本院行冠状动脉造影检查的患者160例,根据其冠状动脉造影检查分为STEMI组和非冠心病对照组,每组80例。记录所有患者临床资料和生化检查指标,采用酶联免疫吸附法检测患者冠状动脉造影检查前血浆HtrA2和细胞色素C(Cyt c)水平。采用受试者工作特征(ROC)曲线、Spearman秩相关分析确定HtrA2与STEMI之间的相关性。结果 STEMI组患者HtrA2、空腹血糖、总胆固醇、低密度脂蛋白胆固醇、肌酸激酶同工酶水平、Gensini评分以及糖尿病、吸烟、Cyt c升高(>0.6 ng/mL)比例(60.0%)均显著高于对照组(均P<0.05)。ROC曲线分析发现,HtrA2预测诊断STEMI的曲线下面积为0.705(95%CI:0.624～0.786,P<0.001)。Spearman秩相关分析显示,患者HtrA2水平与其Gensini评分存在正相关关系(r=0.457,P<0.001)。结论 HtrA2水平增高对STEMI的诊断和病情评估具有一定价值,可能与其涉及细胞线粒体损伤机制有关。
Objective To investigate the change of plasma high-temperature requirement protein A2(HtrA2) level in patients with ST-segment elevation myocardial infarction( STEMI), and evaluate its clinical values for predicting STEMI.Methods One hundred and sixty patients undergoing coronary angiography in People's Hospital of Xinjiang Uygur Autonomous Region were enrolled between January 2017 and December 2017. The patients were divided into STEMI group(n=80) and control group(n=80) according to the results of coronary angiography. Clinical characteristics, routine laboratory parameters and Gensini score were collected. The plasma levels of HtrA2 and cytochrome c(Cyt c) were tested using enzyme-linked immunosorbent assay. Logistic regression, receiver operating characteristic(ROC) curve and Spearman correlations were applied to evaluate the associations between HtrA2 and STEMI. Results In the STEMI group,HtrA2, fasting blood glucose, total cholesterol,low-density lipoprotein cholesterol, creatine kinase isoenzyme levels,Gensini score, and diabetes, smoking, and increased Cyt c( >0.6 ng/mL) ratio(60.0%) were significantly higher than those of the control group(P<0.05). ROC curve analysis found that the area under the curve of HtrA2 predictive diagnosis of STEMI was 0.705(95% CI: 0.624～0.786, P<0.001). Spearman rank correlation analysis showed that there was a positive correlation between HtrA2 level and Gensini score( r=0.457,P<0.001). Conclusion The increase of HtrA2 level has certain value for the diagnosis and disease evaluation of STEMI,which may be related to the mechanism of mitochondrial damage involved in cells.
Objective To investigate the change of plasma high-temperature requirement protein A2(HtrA2) level in patients with ST-segment elevation myocardial infarction( STEMI), and evaluate its clinical values for predicting STEMI.Methods One hundred and sixty patients undergoing coronary angiography in People's Hospital of Xinjiang Uygur Autonomous Region were enrolled between January 2017 and December 2017. The patients were divided into STEMI group(n=80) and control group(n=80) according to the results of coronary angiography. Clinical characteristics, routine laboratory parameters and Gensini score were collected. The plasma levels of HtrA2 and cytochrome c(Cyt c) were tested using enzyme-linked immunosorbent assay. Logistic regression, receiver operating characteristic(ROC) curve and Spearman correlations were applied to evaluate the associations between HtrA2 and STEMI. Results In the STEMI group,HtrA2, fasting blood glucose, total cholesterol,low-density lipoprotein cholesterol, creatine kinase isoenzyme levels,Gensini score, and diabetes, smoking, and increased Cyt c( >0.6 ng/mL) ratio(60.0%) were significantly higher than those of the control group(P<0.05). ROC curve analysis found that the area under the curve of HtrA2 predictive diagnosis of STEMI was 0.705(95% CI: 0.624～0.786, P<0.001). Spearman rank correlation analysis showed that there was a positive correlation between HtrA2 level and Gensini score( r=0.457,P<0.001). Conclusion The increase of HtrA2 level has certain value for the diagnosis and disease evaluation of STEMI,which may be related to the mechanism of mitochondrial damage involved in cells.
引文
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[10]Jing X,Yang J,Jiang L,et al.MicroRNA-29b Regulates the Mitochondria-Dependent Apoptotic Pathway by Targeting Bax in Doxorubicin Cardiotoxicity[J].Cell Physiol Biochem,2018,48(2):692-704.
[11]张梦颖,吕志跃,吴忠道.细胞凋亡发生机制研究进展[J].热带医学杂志,2016,16(10):1346-1349+1352.
[12]Eleftheriadis T,Pissas G,Liakopoulos V,et al.Cytochrome c as a Potentially Clinical Useful Marker of Mitochondrial and Cellular Damage[J].Front Immunol,2016,7:279.
[13]Hortmann M,Robinson S,Mohr M,et al.Circulating HtrA2 as a novel biomarker for mitochondrial induced cardiomyocyte apoptosis and ischemia-reperfusion injury in ST-segment elevation myocardial infarction[J].Int J Cardiol,2017,243:485-491.
[14]Bhuiyan MS,Fukunaga K.Activation of HtrA2,a mitochondrial serine protease mediates apoptosis:current knowledge on HtrA2mediated myocardial ischemia/reperfusion injury[J].Cardiovasc Ther,2008,26(3):224-232.
[15]Wang K,Yuan Y,Liu X,et al.Cardiac Specific Overexpression of Mitochondrial Omi/HtrA2 Induces Myocardial Apoptosis and Cardiac Dysfunction[J].Sci Rep,2016,6:37927.
[16]Sun LL,Zhang L,Meng XL,et al.Effects of fluid shear stress on the expression of Omi/HtrA2 in human umbilical vein endothelial cells[J].Mol Med Rep,2013,7(1):110-114.
[2]Lesnefsky EJ,Chen Q,Tandler B,et al.Mitochondria Dysfunction and Myocardial Ischemia-Reperfusion:Implications for Novel Therapies[J].Annu Rev Pharmacol Toxicol,2017,57:535-565.
[3]Rodrigue-Gervais IG,Doiron K,Champagne C,et al.The mitochondrial protease HtrA2 restricts the NLRP3 and AIM2inflammasomes[J].Sci Rep,2018,8(1):8446.
[4]Wang K,Zhang J,Liu J,et al.Variations in the protein level of Omi/HtrA2 in the heart of aged rats may contribute to the increased susceptibility of cardiomyocytes to ischemia/reperfusion injury and cell death:Omi/HtrA2 and aged heart injury[J].Age(Dordr),2013,35(3):733-746.
[5]Liu X,Lei J,Wang K,et al.Mitochondrial Omi/HtrA2 Promotes Caspase Activation Through Cleavage of HAX-1 in Aging Heart[J].Rejuvenation Res,2017,20(3):183-192.
[6]Marenzi G,Cosentino N,Boeddinghaus J,et al.Diagnostic and Prognostic Utility of Circulating Cytochrome c in Acute Myocardial Infarction[J].Circ Res,2016,119(12):1339-1346.
[7]Lemesle G,Tricot O,Meurice T,et al.Incident Myocardial Infarction and Very Late Stent Thrombosis in Outpatients With Stable Coronary Artery Disease[J].J Am Coll Cardiol,2017,69(17):2149-2156.
[8]严叶香,车文良.院前脉压对STEMI患者MACE发生率及心肌功能血清指标的影响[J].热带医学杂志,2017,17(10):1335-1339.
[9]Shvedova M,Anfinogenova Y,Popov SV,et al.Connexins and Nitric Oxide Inside and Outside Mitochondria:Significance for Cardiac Protection and Adaptation[J].Front Physiol,2018,9:479.
[10]Jing X,Yang J,Jiang L,et al.MicroRNA-29b Regulates the Mitochondria-Dependent Apoptotic Pathway by Targeting Bax in Doxorubicin Cardiotoxicity[J].Cell Physiol Biochem,2018,48(2):692-704.
[11]张梦颖,吕志跃,吴忠道.细胞凋亡发生机制研究进展[J].热带医学杂志,2016,16(10):1346-1349+1352.
[12]Eleftheriadis T,Pissas G,Liakopoulos V,et al.Cytochrome c as a Potentially Clinical Useful Marker of Mitochondrial and Cellular Damage[J].Front Immunol,2016,7:279.
[13]Hortmann M,Robinson S,Mohr M,et al.Circulating HtrA2 as a novel biomarker for mitochondrial induced cardiomyocyte apoptosis and ischemia-reperfusion injury in ST-segment elevation myocardial infarction[J].Int J Cardiol,2017,243:485-491.
[14]Bhuiyan MS,Fukunaga K.Activation of HtrA2,a mitochondrial serine protease mediates apoptosis:current knowledge on HtrA2mediated myocardial ischemia/reperfusion injury[J].Cardiovasc Ther,2008,26(3):224-232.
[15]Wang K,Yuan Y,Liu X,et al.Cardiac Specific Overexpression of Mitochondrial Omi/HtrA2 Induces Myocardial Apoptosis and Cardiac Dysfunction[J].Sci Rep,2016,6:37927.
[16]Sun LL,Zhang L,Meng XL,et al.Effects of fluid shear stress on the expression of Omi/HtrA2 in human umbilical vein endothelial cells[J].Mol Med Rep,2013,7(1):110-114.