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中性粒细胞弹性蛋白酶衍生的纤维蛋白降解产物表明存在腹主动脉瘤,并与管腔内血栓体积相关。

Neutrophil Elastase-Derived Fibrin Degradation Products Indicate Presence of Abdominal Aortic Aneurysms and Correlate with Intraluminal Thrombus Volume.

机构信息

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

出版信息

Thromb Haemost. 2018 Feb;118(2):329-339. doi: 10.1160/TH17-05-0348. Epub 2018 Jan 29.

Abstract

BACKGROUND

The intraluminal thrombi (ILT) of abdominal aortic aneurysms (AAA) contain neutrophils, which can secrete elastase. We evaluated whether plasma neutrophil elastase-derived cross-linked fibrin degradation products (E-XDP) could reveal the presence, size and mechanical stress of AAAs and its ILTs.

METHODS

E-XDP and D-dimer were measured in plasma from 37 male patients with AAA and 42 male controls. The ILT volumes of the AAAs and any coexisting aneurysms could be measured in 29 patients and finite element analysis was performed to estimate mechanical stress of the ILT. E-XDP, neutrophil elastase and neutrophil marker CD66acd were evaluated in aortic tissue with immunohistochemistry (IHC). The association between ILT volume and E-XDP was validated in a separate cohort ( = 51).

RESULTS

E-XDP levels were elevated in patients with AAA compared with controls ( = 5.8e-13), indicated AAA with 98% sensitivity, 86% specificity and increased with presence of coexisting aneurysms. The association between AAA and increased E-XDP was independent of smoking, comorbidities and medication. E-XDP correlated with volume of all ILTs ( = 0.76,  = 4.5e-06), mean ILT stress ( = 0.46,  = 0.013) and the volume of the AAA-associated ILT ( = 0.64,  = 0.00017). E-XDP correlated stronger with ILT volume compared with D-dimer ( = 0.76 vs.  = 0.64,  = 0.018). The correlation between E-XDP and ILT volume was validated in the separate cohort ( = 0.53,  = 7.6e-05). IHC revealed E-XDP expression in the ILT, spatially related to neutrophil elastase and neutrophils.

CONCLUSION

E-XDP is a marker of the presence of AAA and coexisting aneurysms as well as the volume and mechanical stress of the ILT.

摘要

背景

腹主动脉瘤(AAA)的腔内血栓(ILT)含有可分泌弹性蛋白酶的中性粒细胞。我们评估了血浆中性粒细胞弹性蛋白酶衍生的交联纤维蛋白降解产物(E-XDP)是否可以揭示 AAA 和其 ILT 的存在、大小和机械应力。

方法

测量了 37 名男性 AAA 患者和 42 名男性对照者的血浆 E-XDP 和 D-二聚体。29 名患者可测量 AAA 的 ILT 体积和任何共存的动脉瘤,并进行有限元分析以估计 ILT 的机械应力。通过免疫组织化学(IHC)评估主动脉组织中的 E-XDP、中性粒细胞弹性蛋白酶和中性粒细胞标志物 CD66acd。在另一组( = 51)中验证了 ILT 体积与 E-XDP 之间的关联。

结果

与对照组相比,AAA 患者的 E-XDP 水平升高( = 5.8e-13),表明 AAA 的敏感性为 98%,特异性为 86%,且随着共存动脉瘤的存在而增加。AAA 与 E-XDP 升高的关联独立于吸烟、合并症和药物。E-XDP 与所有 ILT 的体积相关( = 0.76,  = 4.5e-06),与平均 ILT 应力相关( = 0.46,  = 0.013),与 AAA 相关的 ILT 体积相关( = 0.64,  = 0.00017)。E-XDP 与 ILT 体积的相关性强于 D-二聚体( = 0.76 与  = 0.64,  = 0.018)。在另一组中验证了 E-XDP 与 ILT 体积之间的相关性( = 0.53,  = 7.6e-05)。IHC 显示 E-XDP 在 ILT 中有表达,与中性粒细胞弹性蛋白酶和中性粒细胞空间相关。

结论

E-XDP 是 AAA 和共存动脉瘤以及 ILT 的体积和机械应力的存在标志物。

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