可溶性人基质裂解素2在评估心力衰竭病情和预后中的作用

doi:10.3969/j.issn.1007-9572.2016.27.023

摘要/Abstract

摘要： 可溶性人基质裂解素2（sST2）是近年发现的重要的心血管疾病血清标志物。近年研究发现，sST2在心力衰竭病理生理学方面存在一定作用，是反映心肌纤维化的指标，亦是心力衰竭新的生物标志物。本文回顾了多项相关研究，分析表明sST2表达水平与心力衰竭的危险分层和预后评估有密切关系，sST2能独立预测心力衰竭预后，有一定临床应用价值。

关键词: 心力衰竭, 可溶性人基质裂解素2, 预后

Abstract: Soluble human stromelysin-2 （sST2） is an important serum marker for cardiovascular disease.Studies have shown that sST2 plays a certain role in the pathophysiology of heart failure,and it is an index for reflecting myocardial fibrosis and a new biomarker for heart failure.In this review,multiple relevant studies were reviewed,and the analysis showed that there is close correlation between sST2 level and heart failure risk stratification and prognosis.sST2 can independently predict the prognosis of heart failure,and has certain clinical application value.

Key words: Heart failure, Soluble human stromelysin-2, Prognosis

胡振, 张新超. 可溶性人基质裂解素2在评估心力衰竭病情和预后中的作用[J]. 中国全科医学, 2016, 19(27): 3375-3379.

HU Zhen, ZHANG Xin-chao. Effect of sST2 in the Assessment of the Disease Condition and Prognosis of Patients with Heart Failure[J]. Chinese General Practice, 2016, 19(27): 3375-3379.

参考文献

［1］JANUZZI J L,MEBAZAA A.ST2 and prognosis in acutely decompensated heart failure:the International ST2 Consensus Panel［J］.Am J Cardiol,2015,115（7 Suppl）:26B-31. ［2］KO D T,TU J V,MASOUDI F A,et al.Quality of care and outcomes of older patients with heart failure hospitalized in the United States and Canada［J］.Arch Intern Med,2005,165（21）：e2486-2492. ［3］程凯,徐峰,陈玉国.2015年欧洲《急性心力衰竭院前和院内早期处理共识》解读［J］.中华急诊医学杂志，2015,24（7）:697-700. ［4］DANIELS L B,MAISEL A S.Natriuretic peptides［J］.JACC，2007，50（25）：2357-2368. ［5］CHEN A A，WOOD M J，KRAUSER D G，et al.NT-proBNP levels，echocardiographic findings，and outcomes in breathless patients：results from the ProBNP investigation of Dyspnea in the Emergency Department （PRIDE） echocardiographic substudy［J］.Euro Heart J，2006，27（7）：839-845. ［6］JANUZZI J L，JR REHMAN S，MUELLER T，et al.Importance of biomarkers for long term mortality prediction in acutely dyspneic patients［J］.Clin Chem，2010，56（12）：1814-1821. ［7］JANUZZI JL J R,SAKHUJA R,O’DONOGHUE M,et al.Utility of aminoterminal pro-brain natriuretic peptide testing for prediction of 1-year mortality in patients with dyspnea treated in the emergency department［J］.Arch Intern Med,2006,166（3）:315-320. ［8］KARAYANNIS G,TRIPOSKIADIS F,SKOULARIGIS J，et al.The emerging role of Galectin-3 and ST2 in heart failure：practical considerations and pitfalls using novel biomarkers［J］.Curr Heart Fail Rep，2013，10（4）：441-449. ［9］MAEDER M T,RICKENBACHER P，RICKI H,et al.N-terminal pro brain natriuretic peptide-guided management in patients with heart failure and preserved ejection fraction:findings from the Trial of Intensified versus standard medical therapy in elderly patients with congestive heart failure （TIME-CHF）［J］.Eur J Heart Fail,2013,15（10）:1148-1156. ［10］LAINCHBURY J G,TROUGHTON R W,FRAMPTON C M,et al.NTproBNP-guided drug treatment for chronic heart failure:design and methods in the "BATTLESCARRED" trial［J］.Eur J Heart Fail,2006,8（5）:532-538. ［11］EURLINGS L M,VAN POL P E,KOK W E,et al.Management of chronic heart failure guided by individual N-terminal pro-B-type natriuretic peptide targets:results of the PRIMA （Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?） study［J］.J Am Coll Cardiol,2010,56（25）:2090-2100. ［12］WEINBERG E O,SHIMPO M,DE KEULENAER G W,et al.Expression and regulation of ST2,an interleukin-1 receptor family member,in cardiomyocytes and myocardial infarction［J］.Circulation,2002,106（23）:2961-2966. ［13］JANUZZI JL J R,PEACOCK W F,MAISEL A S,et al.Measurement of the interleukin family member ST2 in patients with acute dyspnea:results from the PRIDE （Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department） study［J］.J Am Coll Cardiol,2007,50:607-613. ［14］BOISOT S,BEEDE J,ISAKSON S,et al.Serial sampling of ST2 predicts 90-day mortality following destabilized heart failure［J］.J Card Fail,2008,14（9）:732-738. ［15］KY B,FRENCH B,MCCLOSKEY K,et al.High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure［J］.Circ Heart Fail,2011,4（2）:180-187. ［16］石金铮.ST2和hs-CRP在急性冠脉综合征中的诊断价值及其在急性心肌梗死后左室心肌重塑的机制研究［D］.济南：山东大学，2011. ［17］COYLE A J,LLOYD C,TIAN J，et al.Crucial role of the interleukin-1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses［J］.J Exp Med,1999,190（7）：895-902. ［18］YIN H，LI X Y，JIN X B，et al.IL-33 prolongs murine cardiac allograft survival through induction of TH2-type immune deviation［J］.Transplantation,2010,89（10）：1189-1197. ［19］SANADA S,HAKUNO D,HIGGINS L J,et al.IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system［J］.J Clin Invest,2007,117（6）:1538-1549. ［20］SEKI K,SANADA S,KUDINOVA A Y,et al.Interleukin-33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling［J］.Circ Heart Fail,2009,2（6）:684-691. ［21］REHMAN S U,MUELLER T,JANUZZI J L.Characteristics of the novel interleukin family biomarker ST2 in patients with acute heart failure［J］.J Am Coll of Cardiol,2008,52（18）:1458-1465. ［22］PASCUAL-FIGAL D A,MANZANO-FERNANDEZ S,BORONAT M,et al.Soluble ST2,high sensitivity troponin T and N-terminal pro-B-type natriuretic peptide:complementary role for risk stratification in acutely decompensated heart failure［J］.Eur J Heart Fail,2011,13（7）:718-725. ［23］MANZANO-FERNANDEZ S,JANUZZI J L,PASTOR-PEREZ F J,et al.Serial monitoring of soluble interleukin family member ST2 in patients with acutely decompensated heart failure［J］.Cardiology,2012,122（3）:158-166. ［24］SHAH R V,CHEN-TOURNOUX A,PICARD M H,et al.Serum levels of the interleukin-1 receptor family member ST2,cardiac structure and function,and long-term mortality in patients with acute dyspnea［J］.Circ Heart Fail,2009,2（4）:311-319. ［25］PASCUAL-FIGAL D A,ORDONEZ-LLANOS J,TORNEL P L,et al.Soluble ST2 for predicting sudden cardiac death in patients with chronic heart failure and left ventricular systolic dysfunction［J］.J Am Coll Cardiol,2009,54（23）:2174-2179. ［26］GAGGIN H K,SZYMONIFKA J,BHARDWAJ A,et al.Head-to-head comparison of serial soluble ST2,growth differentiation factor-15,and highly-sensitive troponin T measurements in patients with chronic heart failure［J］.JACC Heart Fail,2014,2（1）:65-72. ［27］GRUSON D,LEPOUTRE T,ROUSSEAU M F,et al.Increased soluble ST2 is a stronger predictor of long-term cardiovascular death than natriuretic peptides in heart failure patients with reduced ejection fraction［J］.Int J Cardiol,2014,172（1）:e250-252. ［28］BAYES-GENIS A,DE ANTONIO M,VILA J,et al.Head-to-head comparison of 2 myocardial fibrosis biomarkers for long-term heart failure risk stratification:ST2 versus galectin-3［J］.J Am Col Cardiol,2014,63（2）:158-166. ［29］ZILINSKI J L,SHAH R V,GAGGIN H K,et al.Measurement of multiple biomarkers in advanced stage heart failure patients treated with pulmonary artery catheter guided therapy［J］.Crit Care,2012,16（4）:R135. ［30］GAGGIN H K,MOTIWALA S,BHARDWAJ A,et al.Soluble concentrations of the interleukin receptor family member ST2 and β-blocker therapy in chronic heart failure［J］.Circ Heart Fail,2013,6（6）:1206-1213. ［31］ANAND I S,RECTOR T S,KUSKOWSKI M,et al.Prognostic value of soluble ST2 in the valsartan heart failure trial［J］.Circ Heart Fail,2014,7（3）:418-426. ［32］LAX A,SANCHEZ-MAS J,ASENSIO-LOPEZ M C,et al.Mineralocorticoid receptor antagonists modulate galectin-3 and interleukin-33/ST2 signaling in left ventricular systolic dysfunction after acute myocardial infarction［J］.JACC Heart Fail,2015,3（1）:50-58. ［33］TANG W H,WU Y,GRODIN J L，et al.Prognostic value of baseline and changes in circulating soluble ST2 levels and the effects of nesiritide in acute decompensated heart failure［J］.JACC Heart Fail,2016,4（1）:68-77. ［34］WANG T J,WOLLERT K C,LARSON M G,et al.Prognostic utility of novel biomarkers of cardiovascular stress:the Framingham Heart Study［J］.Circulation,2012,126（13）:1596-1604. ［35］COGLIANESE E E,LARSON M G,VASAN R S,et al.Distribution and clinical correlates of the interleukin receptor family member soluble ST2 in the Framingham Heart Study［J］.Clin Chem,2012，58（12）：1673-1681. ［36］MUELLER T,ZIMMERMANN M,DIEPLINGER B,et al.Comparison of plasma concentrations of soluble ST2 measured by three different commercially available assays:the MBL ST2 assay,the Presage ST2 assay,and the R&D ST2 assay［J］.Clin Chim Acta,2012,13（19/20）:1493-1494. ［37］BAYES-GENIS A,ZHANG Y,KY B.ST2 and patient prognosis in chronic heart failure［J］.Am J Cardiol,2015,115（7 Suppl）:64B-69. ［38］MAISEL A S,RICHARDS A M,PASCUAL-FIGAL D,et al.Serial ST2 testing in hospitalized patients with acute heart failure［J］.Am J Cardiol,2015,115（7 Suppl）:32B-37. ［39］PIPER S E,SHERWOOD R A,AMIN-YOUSSEF G F,et al.Serial soluble ST2 for the monitoring of pharmacologically optimised chronic stable heart failure［J］.Int J Cardiol,2015,178:284-291. ［40］KIM M S,JEONG T D,HAN S B,et al.Role of soluble ST2 as a prognostic marker in patients with acute heart failure and renal insufficiency［J］.J Korean Med Sci,2015,30（5）:569-575. ［41］MEBBAZA A,DI SOMMA S,MAISEL A E,et al.ST2 and multimarker testing in acute decompensated heart failure［J］.Am J Cardiol,2015,115（7 Suppl）:38B-43. ［42］FRI ES F,LOUREN O P,LASZCZYNSKA O,et al.Prognostic value of sST2 added to BNP in acute heart failure with preserved or reduced ejection fraction［J］.Clin Res Cardiol,2015,104（6）:491-499. ［43］VAN KIMMENADE R R,JANUZZI J L.Emerging biomarkers in heart failure［J］.Clin Chem,2012,58（1）:127-138.

[1]	王立娜, 雷警输, 李奎宝, 王睿颖, 李新苗, 王芳芳, 郭晓荣, 牛瑞浩, 赵伟, 周芳芳, 赵京晶, 李忠佑. 急性心肌梗死患者炎症反应研究进展[J]. 中国全科医学, 2026, 29(06): 790-801.
[2]	雷淳心, 张曦亚, 张燕, 陈嘉琪, 刘子菡, 罗静, 陶庆文. 原发性干燥综合征燥瘀互结证患者临床特点及影响因素研究[J]. 中国全科医学, 2026, 29(06): 718-725.
[3]	付积艺, 郑博月, 吴佳霏, 王珺, 李慧. 组蛋白去乙酰化酶抑制剂联合维奈克拉和阿扎胞苷治疗成人急性T淋巴细胞白血病的疗效及安全性研究[J]. 中国全科医学, 2026, 29(04): 483-489.
[4]	王艺衡, 许晓明, 夏云龙, 夏林莺, 韩雪, 郭永珍, 刘泉池, 闫文俊. 射血分数保留的心力衰竭药物治疗进展[J]. 中国全科医学, 2026, 29(03): 403-408.
[5]	江晓蕊, 闫玉瑶, 卫靖靖, 乔利杰, 彭广操, 朱明军. 冠心病患者并发心力衰竭风险预测模型的系统评价[J]. 中国全科医学, 2026, 29(03): 393-402.
[6]	谭洁文, 陈嫦, 钟锦漫, 胡婉贞, 白海, 熊丹. 基于生物信息学分析乳酸代谢对多发性骨髓瘤患者预后及肿瘤微环境的影响研究[J]. 中国全科医学, 2025, 28(36): 4592-4604.
[7]	周倩梅, 缪卡莉, 钟永鸣, 张辅满, 张哲, 李成贻. Gas6在浸润性乳腺癌中的表达及其与临床病理特征和预后相关性研究[J]. 中国全科医学, 2025, 28(35): 4449-4456.
[8]	刘永成, 刘思雨, 梁小雨, 郝校鹏, 魏玥, 董国菊. 射血分数保留型心力衰竭随机对照试验的超声心动图结局指标研究[J]. 中国全科医学, 2025, 28(33): 4140-4147.
[9]	马双双, 邢岩江, 张佳玮, 王婧. 心力衰竭中心脏能量代谢变化研究进展[J]. 中国全科医学, 2025, 28(30): 3831-3840.
[10]	农景堂, 杨成敏, 莫圣龙, 陆志成, 唐丽娜, 简崇东, 商敬伟. 脑梗死预后相关生物标志物的研究新进展：机制与临床应用[J]. 中国全科医学, 2025, 28(29): 3711-3720.
[11]	李仪丙, 贾鸿博, 樊小农, 赵文君, 刘巍, 葛文逸, 李宋姣, 雷康辰, 张梦龙, 张薇薇, 陈阳, 李礼. 卒中后吞咽障碍预后影响因素的综合评估：一项伞形综述[J]. 中国全科医学, 2025, 28(29): 3631-3637.
[12]	邓洁, 齐祺, 吴欣雨, 韩全乐, 李雷, 蒋越, 郁静, 吴若洁, 吴寿岭, 李康博. 血浆致动脉硬化指数与体检人群新发心力衰竭风险的队列研究[J]. 中国全科医学, 2025, 28(29): 3645-3652.
[13]	刘振宇, 魏云鹏, 王江敏, 邢彦. 睡眠时间与心力衰竭的因果关联研究[J]. 中国全科医学, 2025, 28(27): 3441-3446.
[14]	徐艳朋, 黄佩, 张平平, 罗艳, 施晓琪, 吴柳松, 陈艳, 何志旭. 急性T淋巴细胞白血病β-肾上腺素受体的表达情况及临床意义研究[J]. 中国全科医学, 2025, 28(27): 3391-3398.
[15]	刘文洁, 孙煌, 罗薇, 陈旋, 彭云珠, 李锐洁, 马米尔. 可穿戴式心音心电远程监测设备用于心力衰竭的研究[J]. 中国全科医学, 2025, 28(25): 3104-3109.