Skip to main content
NCBI home page
Journal of Southern Medical University logoLink to Journal of Southern Medical University
. 2021 May 20;41(5):710–715. [Article in Chinese] doi: 10.12122/j.issn.1673-4254.2021.05.11

血清ADAMTS13、TSP1与急性冠脉综合征患者心肌损伤和临床预后的相关性

Correlation of serum ADAMTS13 and TSP1 levels with myocardial injury and prognosis in patients with acute coronary syndrome

Zhuoya YAO 1, Bingwei BAO 1, Shaohuan QIAN 1, Zheng LI 1, Qiao LU 1, Shengping MIN 2, Miaonan LI 1,*, Hongju WANG 1,*
PMCID: PMC8214964  PMID: 34134958

Abstract

Objective

To investigate serum levels of von Willebrand factor lytic protease (ADAMTS13) and thrombospondin-1 (TSP1) in patients with different types of acute coronary syndrome (ACS) and their correlation with the patients' clinical prognosis.

Methods

According to their disease history, results of angiography and clinical biochemical tests, a total of 405 patients undergoing coronary angiography, were divided into unstable angina (UAP) group (n=215), acute myocardial infarction (AMI) group (n=96), and angiographically normal group (n=94). Serum ADAMTS13 and TSP1 levels were detected in all the patients, who were followed up for 15 months to evaluate the occurrence of long-term major cardiac adverse events (MACE).

Results

Serum ADAMTS13 level was significantly lower and TSP1 level was significantly higher in AMI group and UAP group than in the normal group (P < 0.001). Serum ADAMTS13 and TSP1 levels were negative correlated in ACS patients (R=-0.577, P < 0.001). The patients experiencing MACE had significantly different serum TSP1 level from those without MACE (P < 0.05). Cox proportion regression model analysis showed that TSP1 was a risk factor affecting the occurrence of MACE in ACS patients; Kaplan-Meier survival analysis showed that the patients with high levels of TSP1 had a higher incidence of longterm MACE than those with low TSP1 levels.

Conclusion

A lowered serum ADAMTS13 level and an elevated TSP1 level can support the diagnosis of ACS. An elevated TSP1 level may serve as an indicator for predicting the risk of MACE in patients with ACS.

Keywords: ADAMTS13, thrombospondin-1, acute coronary syndrome, clinical prognosis

急性冠脉综合征(ACS)是冠心病的一种严重类型，严重威胁着人们的生命健康。动脉粥样硬化是冠心病的共同病理改变，内皮功能障碍则是AS的起始及关键环节[1]。参与内皮功能障碍的机制非常复杂，近年来研究发现，血管性血友病因子(vWF)在冠脉血管壁内皮细胞功能改变的过程中扮演着重要角色[2-3]。当内皮细胞受到刺激或损伤以及机体处于应激状态下vWF释放，并可作为诱导剂首先与血小板表面糖蛋白GPⅡb/Ⅲa结合，诱导血小板的粘附、聚集，促进血小板活化，加剧血液凝固形成血栓[4]。而体内主要调控vWF的酶有血管性血友病因子裂解蛋白酶(ADAMTS13)和凝血酶敏感蛋白1(TSP1)[5]。ADAMTS13可裂解超大相对分子质量vWF为小分子片段；TSP1作为vWF的还原酶，竞争性结合ADAMTS13的A3结构域，进而抑制ADAMTS13对vWF的降解[6-7]。关于ADAMTS13、TSP1与ACS的相关性研究虽有报道[8-10]，但是目前尚无研究证实2种因子表达水平在ACS患者中竞争性抑制关系，且ADAMTS13、TSP1是否为ACS患者PCI术后MACE事件发生的独立危险因素尚未有定论[11-13]。由此，本研究拟以ACS中不稳定型心绞痛(UAP)和急性心肌梗死(AMI)患者为代表，同时以冠状动脉造影正常患者为对照，检测3组受试者血清中ADAMTS13和TSP1的含量，在明确UAP和AMI患者存在内皮损伤的基础上，观察3组受试者ADAMTS13和TSP1水平与临床预后，从临床角度探讨ADAMTS13、TSP1与UAP和AMI的相关性并为ACS患者的病情评估、新药研发和个体化治疗提供新的理论基础。

1. 资料和方法

1.1. 研究对象

本研究为前瞻性单中心观察性研究，选取2018年10月~2019年7月入住蚌埠医学院第一附属医院并接受冠状动脉造影检查者401例。纳入标准：参照中华医学会心血管病学分会相关指南[14-15]，根据病史、造影结果和临床生化指标分为：不稳定型心绞痛组(UAP组，n=215)、急性心肌梗死组(AMI组，n=94)；并选取同期因胸痛入住我院心内科但经冠脉造影检查排除为冠心病的患者为Control组(n=92)。排除标准：合并如先天性心脏病、严重心脏瓣膜疾病、心肌病等其他心脏疾病的患者；碘或碘造影剂过敏患者；并发或短期内存在严重肝肾功能不全、肿瘤、血液系统疾病、免疫性疾病、急性感染性疾病及其他消耗性疾病等；病史资料收集不全患者。本研究所纳入患者均知情同意，并经本医院伦理委员会审核。

1.2. 研究方法

清晨或急诊冠脉介入术前采集受试者空腹外周静脉血约5 mL，部分送至我院检验科行血常规、生化常规、肝肾功能等项目检查，部分经2500×g离心5 min后收集上层血清，-80 ℃冻存备用。严格按照ELISA试剂盒说明书的步骤进行操作，最后在酶标仪上读取吸光度值A450 nm，求平均值并建立标准曲线，按照得出的公式计算出对应样品血清中的ADAMTS13、TSP1含量。冠状动脉造影由我院心血管内科专业医师操作完成，采用2001年美国ACC/AHA关于心血管疾病诊断和治疗标准判断结果，依据Gensini评分结合患者冠状动脉造影检查结果定量计算血管病变狭窄程度[16-17]。

1.3. 术后随访

所有患者出院后平均随访15月(15±2月)，随访终点事件为主要心血管不良事件(MACE)，包括再发胸痛、心力衰竭、脑卒中、再发心梗、出血、再次血运重建、支架内血栓、支架内再狭窄、死亡[18-19]。

1.4. 统计学处理

采用IBM SPSS Statistics 26.0统计软件包对数据进行分析处理。计量资料用均数±标准差表示，正态分布资料采用方差分析，非正态分布资料采用非参数检验。分类资料的描述采用构成比，比较采用χ2检验。相关性分析采用了Pearson相关分析。ADAMTS13、TSP1与ACS患者术后MACE发生之间的关系采用Cox比例风险回归模型进行分析，预测MACE发生的截断值采用ROC曲线评定。采用Kaplan-Meier生存分析来比较两组患者的远期生存情况。P < 0.05为差异有统计学意义。

2. 结果

2.1. 一般临床资料比较

401例患者中男性241例(60.1%)，女性160例(39.9%)，平均年龄64.7±10.3岁。基线资料显示各组尿酸(UA)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、血小板水平差异均无统计学意义(P>0.05)；AMI、UAP组年龄、甘油三酯(TG)较Control显著升高(P < 0.05)；AMI组血肌酐(SCr)、高密度脂蛋白胆固醇(HDL-C)、C反应蛋白(CRP)、白细胞较UAP组和Control组显著升高(P < 0.05，表 1)。

1.

患者基本临床资料

General clinical data of the patients (Mean±SD)

Items Control group (n=92) UAP group (n=215) AMI group (n=94) t/χ2 P
UAP: Unstable angina; AMI: Acute myocardial infarction; GLU: Blood glucose; UA: Uric acid; SCr: Serum creatinine; TC: Total cholesterol; TG: Triglyceride; LDL-C: Low-density lipoprotein cholesterol; HDL-C: High-density lipoprotein cholesterol; CRP: Creactive protein; WBC: Leukocyte; LVEF: Left ventricular ejection fraction. *P < 0.05 vs control; #P < 0.05 vs UAP.
Age (year) 56.00 (49.00, 63.25) 67.00 (57.00, 73.00)* 64 (56.00, 70.50)* 54.346 0.000
Male (n, %) 37 (0.39) 132 (0.61) 74 (0.79) 32.323 0.000
Hypertension (n, %) 44 (0.46) 149 (0.69) 54 (0.57) 16.009 0.000
DM (n, %) 10 (0.10) 66 (0.31) 24 (0.26) 14.727 0.001
GLU (mmol/L) 4.95 (4.49, 5.61) 4.97 (4.45, 6.75) 6.03 (4.91, 8.33) 19.113 0.000
UA (µmol/L) 301.62±81.26 316.67±87.35 332.39±107.56 2.636 0.073
SCr (µmol/L) 65.00 (58.75, 69.25) 68.00 (63.00, 74.00) 72.00 (64.00, 89.50))*# 19.503 0.000
TC (mmol/L) 3.85 (3.16, 4.70) 3.80 (3.20, 4.75) 3.56 (3.18, 4.85) 0.110 0.946
TG (mmol/L) 1.34 (0.90, 1.78) 1.47 (1.08, 2.06)* 1.68 (1.17, 2.40)* 12.165 0.002
LDL-C (mmol/L) 2.12 (1.64, 2.76) 2.03 (1.61, 2.66) 2.03 (1.67, 2.76) 1.213 0.545
HDL-C (mmol/L) 0.95 (0.83, 1.18) 0.89 (0.75, 1.03)* 0.85 (0.73, 0.99)*# 12.466 0.002
CRP (mg/L) 1.30 (0.53, 2.58) 1.40 (0.66, 3.70) 2.60 (0.66, 5.66)*# 20.563 0.000
WBC (×109 /L) 5.72 (5.05, 6.73) 6.14 (5.41, 7.5) 7.20 (5.76, 9.66)*# 23.539 0.000
LVEF (%) 59.00 (55.00, 62.00) 56.00 (53.00, 60.00) 54.00 (47.00, 56.50)* 27.184 0.000
Gensini Score - 26.00 (10.00, 46.00) 42.50 (26.25, 75.50) # 1.507 0.000
Open in a new tab

2.2. 外周血清ADAMTS13、TSP1水平变化

在不同性别、有无高血压、有无糖尿病组间ADAMTS13、TSP1均无统计学差异(P>0.05)。与对照组相比，UAP组和AMI组患者血清TSP1水平升高(P < 0.001)；且AMI组较UAP组TSP1水平进一步升高，但差别无统计学意义(P>0.05，图 1A)。UAP组和AMI组患者血清中ADAMTS13水平较对照组降低(P < 0.001)；AMI组血清中ADAMTS13水平较UAP组进一步降低，但差别无统计学意义(P>0.05，图 1B)。

1.

1

Open in a new tab

各组患者TSP1和ADAMTS13水平比较

TSP1 (A) and ADAMTS13 (B) levels in angiographically normal patients and patients with UAP and AMI. TSP1: Thrombospondin-1; ADAMTS13: A disintegrin and metalloproteinase with thrombospondin type 1 motif 13. *P < 0.001.

2.3. ADAMTS13、TSP1在ACS患者血清中的相关性

当ADAMTS13水平降低时TSP1的含量显著升高，两者呈负相关(R=-0.577，P < 0.001，图 2)。

2.

2

Open in a new tab

ADAMTS13与TSP1的相关性分析

Correlation analysis betweenADAMTS13 and TSP1.

2.4. ACS患者MACE组与非MACE组患者冠脉病变程度比较

309名ACS患者共8人失访。结果显示MACE组TSP1、Gensini评分、合并糖尿病比例较非MACE组显著升高(P < 0.05)，而ADAMTS13水平、年龄、性别、高血压、UA、SCr、TC、TG、HDL、LDL、CRP、LVEF未见明显差异(P>0.05，表 2)。

2.

MACE组与非MACE组患者基线资料比较

Baseline characteristics of MACE group and non-MACE group (Mean±SD)

Variable MACE group (n=39) Non MACE group (n=262) F or χ2 P
TSP1 (ng/mL) 24.82 (18.61, 34.91) 22.88 (15.39, 28.72) 2.135 0.033
ADAMTS13 (ng/mL) 970.63 (593.13, 1158.13) 1013.44 (669.69, 1358.91) 1.148 0.251
Gensini score 41.50 (18.75, 79.00) 30.00 (12.00, 50.00) 2.480 0.013
Age (years) 64.00 (57.00, 71.00) 66.00 (56.00, 72.00) 1.258 0.208
Male (n, %) 31 (0.79) 174 (0.66) 2.672 0.102
Hypertension (n, %) 23 (0.59) 176 (0.67) 1.019 0.313
DM (n, %) 18 (0.46) 69 (0.26) 6.488 0.011
GLU (mmol/L) 6.01 (4.78, 8.01) 5.04 (4.50, 6.54) 6.002 0.014
UA (µmol/L) 309.00 (228.00, 385.00) 310.00 (258.25, 374.75) 0.418 0.676
SCr (µmol/L) 69.00 (61.00, 79.00) 68.00 (64.00, 75.00) 0.104 0.917
TC (mmol/L) 3.84 (3.13, 4.56) 3.73 (3.17, 4.79) 0.392 0.695
TG (mmol/L) 1.28 (0.99, 1.70) 1.54 (1.13, 2.10) 1.562 0.118
HDL-C (mmol/L) 0.90 (0.76, 1.01) 0.87 (0.74, 1.02) 0.178 0.859
LDL-C (mmol/L) 2.15 (1.54, 2.86) 2.00 (1.63, 2.71) 1.390 0.165
CRP (mg/L) 2.60 (0.77, 8.90) 1.50 (0.61, 3.88) 1.897 0.058
LVEF (%) 55.00 (50.00, 59.00) 56.00 (53.00, 60.00) 1.527 0.127
Open in a new tab

2.5. Cox比例危险回归模型分析

选取MACE组与非MACE组基线资料存在差异的TSP1、GLU，采用Cox比例危险回归模型进行分析结果显示，随着ACS患者术前TSP1、GLU水平升高，ACS患者术后MACE事件发生风险在不同模型中均相应显著增加(表 3)。

3.

Cox比例危险回归模型分析

Cox proportional hazard model

Model TSP1 GLU
HR (95% CI) P HR (95% CI) P
Model 1: TSP1/GLU; Model 2: Model 1+Age, Male; Model 3: Model 2+Hypertension, DM, UA, SCr, TC, TG, HDL, LDL, CRP, LVEF.
Model 1 1.039 (1.007-1.072) 0.017 1.068 (1.009-1.130) 0.023
Model 2 1.040 (1.008-1.073) 0.013 1.078 (1.015-1.145) 0.014
Model 3 1.047 (1.003-1.092) 0.035 1.095 (0.971-1.234) 0.139
Open in a new tab

2.6. ROC曲线和Kaplan-Meier生存分析

ROC曲线分析显示，预测ACS患者术后MACE事件发生的TSP1、GLU截断值分别为31.27 ng/mL、5.89mmol/L。K-M曲线显示，TSP1水平大于31.27ng/mL、GLU水平大于5.89 mmol/L的患者较小于组患者MACE事件发生风险更高(P=0.001，图 3)。

3.

3

Open in a new tab

KM曲线分析TSP1与GLU对ACS患者MACE预测价值

Kaplan-Meier survival analysis of the value of TSP1 and GLU for predicting MACE in ACS patients. A: Kaplan-Meier survival curves of patients with TSP1 level above 31.27 ng/mL and below 31.27 ng/mL; B: Kaplan-Meier survival curves of patients GLU level above 5.89 mm/L and below 5.89 mm/L.

3. 讨论

当前冠心病发病率持续上升，并呈现年轻化趋势，对人们的生命和健康带来严重威胁。既往流行病学调查研究发现，中国冠心病患者数量达1100万左右，且这一数值还在全社会范围内呈现上升趋势[20]。由此，从发病机制研究疾病相关的血清标志物水平变化，观察相关标志物水平与ACS患者预后关系，对于寻找延缓或逆转冠状动脉粥样硬化的进展、提供个体化治疗及新的治疗思路具有重要作用。

ADAMTS13是一种主要由肝星状细胞分泌的金属蛋白酶，其主要生理功能是裂解血管损伤期间释放的ul-vWF，减少其在血管内皮表面的沉积，并将其切割成较小的、活性较低的片段释放到循环中，从而减少血小板与ul-vWF或vWF在血管内皮细胞的黏附，延缓动脉粥样硬化形成[21]。TSP1作为vWF一种重要还原酶，可通过切断vWF多聚体中的二硫键来降低vWF多聚体的大小，并通过与ADAMTS13竞争性地结合vWF的A2和A3区，与ADAMTS13共同调控vWF的降解[5]。既往有临床资料显示，血清ADAMTS13、TSP1可能通过炎症反应、冠脉内皮损伤、介导血小板的初始粘附等机制影响动脉粥样硬化形成[22-25]。本研究发现UAP、AMI组患者外周血清中ADAMTS13的含量明显降低，TSP1的含量明显升高，ACS患者血清ADAMTS13水平与TSP1水平呈显著负相关，提示在vWF介导的ACS患者急性冠脉损伤中，ADAMTS13、TSP1水平对ACS患者粥样斑块的恶性进展和转归共同产生影响。据此，针对ADAMTS13、TSP1水平变化进而减少冠状动脉狭窄部位vWF介导的血小板粘附和凝集的治疗方案为可为ACS的治疗提供新的思路[26-27]。

在大部分ACS患者预后不良的前提下，如何对ACS患者进行更有效的风险评估是有待于深入研究的临床重要问题。Tscharre等[28]对接受PCI治疗的701例患者进行8年的随访发现ADAMTS13水平与ACS患者与稳定性冠心病(SCAD)患者患者术后长期MACE事件发生均无相关意义。Kaiser等[11]发现PCI术后TSP1水平的降低可作为ST段抬高型心肌梗死患者PCI术后MACE事件发生的预测指标。但目前对术前ADAMTS13、TSP1水平与接受PCI治疗后患者预后关系仍未有定论。本研究对309例ACS患者进行了平均15月的随访，结果显示MACE组患者TSP1、Gensini评分、合并糖尿病比例、入院血糖水平较非MACE组显著升高，较高的TSP1、血糖水平、冠脉病变程度、合并糖尿病可能是MACE组患者重要特征。Cox风险比例回归分析及KM曲线显示，在不同模型中，TSP1较入院血糖水平能较好预测ACS患者术后MACE发生风险；当TSP1值≥31.27 ng/mL时，患者MACE发生风险显著增加。Kaiser等[29]研究发现，造成MACE组TSP1水平的差异可能与PCI术后冠脉血管疏通血清TSP1水平迅速下降有关，结合本研究结果，可有针对性的通过ACS患者术前TSP1水平有效识别ACS高危预后患者，进而有目的性地监控该部分患者预后状态，有效控制其MACE发生概率，提高患者生存时间及生存质量。另一方面，在本研究中，ACS患者入院血糖水平虽然较TSP1不能更好预测ACS患者术后MACE发生风险，且入院血糖可能因采集血清标本时空腹与急查非空腹等混杂因素不能较好反映患者血糖控制水平，但糖尿病作为冠心病的等危性疾病，在今后临床工作中我们要加强对于血糖水平控制不佳的ACS患者重视程度，进而有效控制其MACE事件发生率[30-31]。

综上所述，本研究证实了ADAMTS13、TSP1在ACS与造影正常患者中的表达量不同，且TSP1是ACS患者PCI术后MACE发生的独立危险因素，提示二者在ACS发病中可能存在不同的作用或调控机制，未来寻找或设计改变TSP1表达的方法或途径，可能为冠心病的临床治疗提供新思路及策略。

Biography

姚卓亚，硕士，住院医师，E-mail: 310109198@qq.com

Funding Statement

国家自然科学基金（81970313）；512人才培育计划（by51201317，by51201105）；心血管损伤与保护基础与临床应用创新团队（BYKC201906）；蚌埠医学院科技创新团队（BYKC201901）；蚌埠医学院自然科学研究重点项目（2020byzd109）

Supported by National Natural Science Foundation of China (81970313)

Contributor Information

姚 卓亚 (Zhuoya YAO), Email: 310109198@qq.com.

李 妙男 (Miaonan LI), Email: 524760484@qq.com.

王 洪巨 (Hongju WANG), Email: hongjuwang1@sina.com.

References

  • 1.Bozic M, Álvarez Á, de Pablo C, et al. Impaired vitamin D signaling in endothelial cell leads to an enhanced leukocyte-endothelium interplay: implications for atherosclerosis development. PLoS One. 2015;10(8):e0136863. doi: 10.1371/journal.pone.0136863. [Bozic M, Álvarez Á, de Pablo C, et al. Impaired vitamin D signaling in endothelial cell leads to an enhanced leukocyte-endothelium interplay: implications for atherosclerosis development[J]. PLoS One, 2015, 10(8): e0136863.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Howes JM, Knäuper V, Malcor JD, et al. Cleavage by MMP-13 renders VWF unable to bind to collagen but increases its platelet reactivity. J Thromb Haemost. 2020;18(4):942–54. doi: 10.1111/jth.14729. [Howes JM, Knäuper V, Malcor JD, et al. Cleavage by MMP-13 renders VWF unable to bind to collagen but increases its platelet reactivity[J]. J Thromb Haemost, 2020, 18(4): 942-54.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Li QM, Zhang ZF, Du RQ, et al. Association analysis between endothelial function related factors and coronary artery Stenosis degree in coronary heart disease patients with type 2 diabetes mellitus. http://www.ncbi.nlm.nih.gov/pubmed/23155698/ J Pediatr Endocrinol Metab. 2012;25(7/8):711–6. doi: 10.1515/jpem-2012-0159. [Li QM, Zhang ZF, Du RQ, et al. Association analysis between endothelial function related factors and coronary artery Stenosis degree in coronary heart disease patients with type 2 diabetes mellitus[J]. J Pediatr Endocrinol Metab, 2012, 25(7/8): 711-6.] [DOI] [PubMed] [Google Scholar]
  • 4.Fredrickson BJ, Dong JF, McIntire LV, et al. Shear-dependent rolling on von Willebrand factor of mammalian cells expressing the platelet glycoprotein Ib-IX-V complex. Blood. 1998;92(10):3684–93. doi: 10.1182/blood.V92.10.3684. [Fredrickson BJ, Dong JF, McIntire LV, et al. Shear-dependent rolling on von Willebrand factor of mammalian cells expressing the platelet glycoprotein Ib-IX-V complex[J]. Blood, 1998, 92(10): 3684-93.] [DOI] [PubMed] [Google Scholar]
  • 5.Wang AY, Liu F, Dong NZ, et al. Thrombospondin-1 and ADAMTS13 competitively bind to VWF A2 and A3 domains in vitro. http://europepmc.org/abstract/MED/20705333. Thromb Res. 2010;126(4):e260-5. doi: 10.1016/j.thromres.2010.07.009. [Wang AY, Liu F, Dong NZ, et al. Thrombospondin-1 and ADAMTS13 competitively bind to VWF A2 and A3 domains in vitro[J]. Thromb Res, 2010, 126(4): e260-5.] [DOI] [PubMed] [Google Scholar]
  • 6.Pedrazzini G, Biasco L, Sulzer I, et al. Acquired intracoronary ADAMTS13 deficiency and VWF retention at sites of critical coronary Stenosis in patients with STEMI. Blood. 2016;127(23):2934–6. doi: 10.1182/blood-2015-12-688010. [Pedrazzini G, Biasco L, Sulzer I, et al. Acquired intracoronary ADAMTS13 deficiency and VWF retention at sites of critical coronary Stenosis in patients with STEMI[J]. Blood, 2016, 127(23): 2934-6.] [DOI] [PubMed] [Google Scholar]
  • 7.Chistiakov D, Melnichenko A, Myasoedova V, et al. Throm-bospondins: a role in cardiovascular disease. Int J Mol Sci. 2017;18(7):1540. doi: 10.3390/ijms18071540. [Chistiakov D, Melnichenko A, Myasoedova V, et al. Throm-bospondins: a role in cardiovascular disease[J]. Int J Mol Sci, 2017, 18(7): 1540.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Al-Masri AA, Habib SS, Hersi A, et al. Effect of acute myocardial infarction on a disintegrin and metalloprotease with thrombospondin motif 13 and von willebrand factor and their relationship with markers of inflammation. Int J Vasc Med. 2020;11(5):4981092. doi: 10.1155/2020/4981092. [Al-Masri AA, Habib SS, Hersi A, et al. Effect of acute myocardial infarction on a disintegrin and metalloprotease with thrombospondin motif 13 and von willebrand factor and their relationship with markers of inflammation[J]. Int J Vasc Med, 2020, 11(5): 4981092.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.罗 林锋, 朱 志标. 冠心病患者血清ADAMTS-1、ADAMTS-13含量与斑块性质、炎症及脂肪因子的相关性. https://www.cnki.com.cn/Article/CJFDTOTAL-HNYY201804004.htm. 海南医学院学报. 2018;24(4):444–7. [罗林锋, 朱志标. 冠心病患者血清ADAMTS-1、ADAMTS-13含量与斑块性质、炎症及脂肪因子的相关性[J]. 海南医学院学报, 2018, 24 (4): 444-7.] [Google Scholar]
  • 10.Kessler T, Zhang L, Liu ZY, et al. ADAMTS-7 inhibits re-endothelialization of injured arteries and promotes vascular remodeling through cleavage of thrombospondin-1. Circulation. 2015;131(13):1191–201. doi: 10.1161/CIRCULATIONAHA.114.014072. [Kessler T, Zhang L, Liu ZY, et al. ADAMTS-7 inhibits re-endothelialization of injured arteries and promotes vascular remodeling through cleavage of thrombospondin-1[J]. Circulation, 2015, 131(13): 1191-201.] [DOI] [PubMed] [Google Scholar]
  • 11.Kaiser R, Grotemeyer K, Kälsch T, et al. Decreased TSP-1 following percutaneous coronary intervention is associated with major adverse cardiac events in ST-elevation myocardial infarction. Clin Hemorheol Microcirc. 2013;54(1):59–73. doi: 10.3233/CH-2012-1565. [Kaiser R, Grotemeyer K, Kälsch T, et al. Decreased TSP-1 following percutaneous coronary intervention is associated with major adverse cardiac events in ST-elevation myocardial infarction[J]. Clin Hemorheol Microcirc, 2013, 54(1): 59-73.] [DOI] [PubMed] [Google Scholar]
  • 12.Lasom S, Komanasin N, Settasatian N, et al. Protective effect of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 haplotype on coronary artery disease. Blood Coagulation Fibrinolysis. 2017;28(4):286–94. doi: 10.1097/MBC.0000000000000594. [Lasom S, Komanasin N, Settasatian N, et al. Protective effect of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 haplotype on coronary artery disease[J]. Blood Coagulation Fibrinolysis, 2017, 28(4): 286-94.] [DOI] [PubMed] [Google Scholar]
  • 13.Bongers TN, de Bruijne EL, Dippel DW, et al. Lower levels of ADAMTS13 are associated with cardiovascular disease in young patients. Atherosclerosis. 2009;207(1):250–4. doi: 10.1016/j.atherosclerosis.2009.04.013. [Bongers TN, de Bruijne EL, Dippel DW, et al. Lower levels of ADAMTS13 are associated with cardiovascular disease in young patients[J]. Atherosclerosis, 2009, 207(1): 250-4.] [DOI] [PubMed] [Google Scholar]
  • 14.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 非ST段抬高型急性冠状动脉综合征诊断和治疗指南(2016) 中华心血管病杂志. 2017;45(5):359–76. doi: 10.3760/cma.j.issn.0253-3758.2017.05.003. [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. 非ST段抬高型急性冠状动脉综合征诊断和治疗指南(2016)[J]. 中华心血管病杂志, 2017, 45(5): 359-76.] [DOI] [PubMed] [Google Scholar]
  • 15.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) https://www.cnki.com.cn/Article/CJFDTOTAL-GWXX201504001.htm. 中华心血管病杂志. 2019;10(47):766–83. doi: 10.3760/cma.j.issn.0253-3758.2019.10.003. [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, 10(47): 766-83.] [DOI] [PubMed] [Google Scholar]
  • 16.Alpert E J, Kuntz A R, Dove C J, et al. ACC/AHA guidelines of percutaneous coronary interventions (revision of the 1993 PTCA guidelines)--executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty) J Am Coll Cardiol. 2001;37(8):2215–39. doi: 10.1016/S0735-1097(01)01344-4. [Alpert E J, Kuntz A R, Dove C J, et al. ACC/AHA guidelines of percutaneous coronary interventions (revision of the 1993 PTCA guidelines)--executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty)[J]. J Am Coll Cardiol, 2001, 37(8): 2215-39.] [DOI] [PubMed] [Google Scholar]
  • 17.Gensini G G. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol. 1983;51(3):606. doi: 10.1016/S0002-9149(83)80105-2. [Gensini G G. A more meaningful scoring system for determining the severity of coronary heart disease[J]. Am J Cardiol, 1983, 51(3): 606.] [DOI] [PubMed] [Google Scholar]
  • 18.Baluja A, Rodríguez-Mañero M, Cordero A, et al. Prediction of major adverse cardiac, cerebrovascular events in patients with diabetes after acute coronary syndrome. http://www.researchgate.net/publication/337969021_Prediction_of_major_adverse_cardiac_cerebrovascular_events_in_patients_with_diabetes_after_acute_coronary_syndrome. Diab Vasc Dis Res. 2020;17(1):1479164119892137. doi: 10.1177/1479164119892137. [Baluja A, Rodríguez-Mañero M, Cordero A, et al. Prediction of major adverse cardiac, cerebrovascular events in patients with diabetes after acute coronary syndrome[J]. Diab Vasc Dis Res, 2020, 17(1): 1479164119892137.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1151–210. doi: 10.1016/S0140-6736(17)32152-9. [GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016[J]. Lancet, 2017, 390(10100): 1151-210.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.胡 盛寿, 高 润霖, 刘 力生, et al. 《中国心血管病报告2018》概要. 中国循环杂志. 2019;34(03):209–20. doi: 10.3969/j.issn.1000-3614.2019.03.001. [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(03), 34: 209-20.] [DOI] [Google Scholar]
  • 21.Gandhi C, Khan MM, Lentz SR, et al. ADAMTS13 reduces vascular inflammation and the development of early atherosclerosis in mice. Blood. 2012;119(10):2385–91. doi: 10.1182/blood-2011-09-376202. [Gandhi C, Khan MM, Lentz SR, et al. ADAMTS13 reduces vascular inflammation and the development of early atherosclerosis in mice[J]. Blood, 2012, 119(10): 2385-91.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Chen J, Chung DW. Inflammation, von Willebrand factor, and ADAMTS13. Blood. 2018;132(2):141–7. doi: 10.1182/blood-2018-02-769000. [Chen J, Chung DW. Inflammation, von Willebrand factor, and ADAMTS13[J]. Blood, 2018, 132(2): 141-7.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Popa M, Tahir S, Elrod J, et al. Role of CD40 and ADAMTS13 in von Willebrand factor-mediated endothelial cell-platelet-monocyte interaction. PNAS. 2018;115(24):E5556–65. doi: 10.1073/pnas.1801366115. [Popa M, Tahir S, Elrod J, et al. Role of CD40 and ADAMTS13 in von Willebrand factor-mediated endothelial cell-platelet-monocyte interaction[J]. PNAS, 2018, 115(24): E5556-65.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Tong X, Khandelwal AR, Qin Z, et al. Role of smooth muscle Nox4-based NADPH oxidase in neointimal hyperplasia. http://smartsearch.nstl.gov.cn/paper_detail.html?id=b378bc0f185c26af95cad2997a104df2. J Mol Cell Cardiol. 2015;89(pt b):185–94. doi: 10.1016/j.yjmcc.2015.11.013. [Tong X, Khandelwal AR, Qin Z, et al. Role of smooth muscle Nox4-based NADPH oxidase in neointimal hyperplasia[J]. J Mol Cell Cardiol, 2015, 89(pt b): 185-94.] [DOI] [PubMed] [Google Scholar]
  • 25.Tong X, Khandelwal AR, Wu X, et al. Pro-atherogenic role of smooth muscle Nox4-based NADPH oxidase. J Mol Cell Cardiol. 2016;92:30–40. doi: 10.1016/j.yjmcc.2016.01.020. [Tong X, Khandelwal AR, Wu X, et al. Pro-atherogenic role of smooth muscle Nox4-based NADPH oxidase[J]. J Mol Cell Cardiol, 2016, 92: 30-40.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Abdelgawwad MS, Cao W, Zheng L, et al. Transfusion of platelets loaded with recombinant ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 repeats-13) is efficacious for inhibiting arterial thrombosis associated with thrombotic thrombocytopenic Purpura. Arterioscler Thromb Vasc Biol. 2018;38(11):2731–43. doi: 10.1161/ATVBAHA.118.311407. [Abdelgawwad MS, Cao W, Zheng L, et al. Transfusion of platelets loaded with recombinant ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 repeats-13) is efficacious for inhibiting arterial thrombosis associated with thrombotic thrombocytopenic Purpura[J]. Arterioscler Thromb Vasc Biol, 2018, 38(11): 2731-43.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Kleiman NS. VWF, ADAMTS13, and acute coronary syndromes. Blood. 2016;127(23):2788–9. doi: 10.1182/blood-2016-04-709550. [Kleiman NS. VWF, ADAMTS13, and acute coronary syndromes[J]. Blood, 2016, 127(23): 2788-9.] [DOI] [PubMed] [Google Scholar]
  • 28.Tscharre M, Tentzeris I, Vogel B, et al. Von Willebrand Factor and ADAMTS13 and long-term outcomes in patients undergoing percutaneous coronary intervention. http://www.sciencedirect.com/science/article/pii/S0049384820304564. Thromb Res. 2020;196(12):31–7. doi: 10.1016/j.thromres.2020.08.018. [Tscharre M, Tentzeris I, Vogel B, et al. Von Willebrand Factor and ADAMTS13 and long-term outcomes in patients undergoing percutaneous coronary intervention[J]. Thromb Res, 2020, 196(12): 31-7.] [DOI] [PubMed] [Google Scholar]
  • 29.Befekadu R, Christiansen K, Larsson A, et al. Increased plasma cathepsin S and trombospondin-1 in patients with acute ST-segment elevation myocardial infarction. Cardiol J. 2019;26(4):385–93. doi: 10.5603/CJ.a2018.0030. [Befekadu R, Christiansen K, Larsson A, et al. Increased plasma cathepsin S and trombospondin-1 in patients with acute ST-segment elevation myocardial infarction[J]. Cardiol J, 2019, 26(4): 385-93.] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Deedwania P, Acharya T, Kotak K, et al. Compliance with guideline-directed therapy in diabetic patients admitted with acute coronary syndrome: Findings from the american heart association's get with the guidelines-coronary artery disease (GWTG-CAD) program. http://smartsearch.nstl.gov.cn/paper_detail.html?id=2807113aac2ad07bfc8e7602210f7b81. Am Heart J. 2017;187(5):78–87. doi: 10.1016/j.ahj.2017.02.025. [Deedwania P, Acharya T, Kotak K, et al. Compliance with guideline-directed therapy in diabetic patients admitted with acute coronary syndrome: Findings from the american heart association's get with the guidelines-coronary artery disease (GWTG-CAD) program[J]. Am Heart J, 2017, 187(5): 78-87.] [DOI] [PubMed] [Google Scholar]
  • 31.Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statistics-2021 update: a report from the American heart association. Circulation. 2021;143(8):e254–e743. doi: 10.1161/CIR.0000000000000950. [Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statistics-2021 update: a report from the American heart association[J]. Circulation, 2021, 143(8): e254-e743.] [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Southern Medical University are provided here courtesy of Editorial Department of Journal of Southern Medical University

RESOURCES