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糖化和氧化应激与ST段抬高型心肌梗死糖尿病患者的血栓成分改变有关。

Glycative and oxidative stress are associated with altered thrombus composition in diabetic patients with ST-elevation myocardial infarction.

作者信息

Sambola Antonia, Ruiz-Meana Marisol, Barba Ignasi, Del Blanco Bruno García, Barrabés José A, Lip G Y, Vilardosa Úrsula, Sansaloni Sara, Rello Pau, García-Dorado David

机构信息

Department of Cardiology, Universitat Autònoma de Barcelona, Barcelona, Spain.

Laboratory of Experimental Cardiology, Universitat Autònoma de Barcelona, Barcelona, Spain.

出版信息

Int J Cardiol. 2017 Sep 15;243:9-14. doi: 10.1016/j.ijcard.2017.04.089.

Abstract

BACKGROUND

The role of type 2 diabetes (T2DM) on composition of thrombus has not been fully characterized in patients with ST-elevation myocardial infarction (STEMI).

AIMS

To elucidate the differences between diabetic and non-diabetic patients with STEMI in relation to the composition of coronary thrombus, and the potential association of these differences with glycated haemoglobin levels and markers of oxidative stress.

METHODS

Intracoronary thrombi from consecutive thrombus aspiration procedures in STEMI patients, 25 diabetic and 28 non-diabetic, were analyzed by immunofluorescence with confocal microscopy. Plasma biomarkers (P-selectin, vWF, PAI-1, t-PA, D-dimer, TF pathway markers, plasmin and CD34) were measured in peripheral blood, and the oxidative capacity of plasma as indirect measure of oxidative stress was measured in parallel.

RESULTS

Patients with T2DM had higher levels of fibrin (P=0.03), P-selectin (P=0.0001), PAI-1 (P=0.03) and vWF (P=0.006) in the thrombus and higher plasma TF activity (P=0.01) compared to non-diabetics. TF activity and plasmin correlated with HbAC levels (R=0.71, P=0.0001; R=0.46, P=0.04, respectively) and TF was inversely correlated with TFPI (R=-0.44, P=0.008) and tPA (R=-0.48, P=0.003). Diabetic patients showed a higher oxidative response of plasma (26.47±6.88% vs 22.06±6.96% of oxidized lipids, P=0.04) (measured by H-NMR spectroscopy) that was associated to increased fibrin content into thrombus (R=0.76, P=0.01).

CONCLUSION

Diabetic patients with STEMI display an increased thrombogenicity that results in a different thrombus composition respect to non-diabetic patients with STEMI. The increased thrombogenicity present in T2DM is related to higher glycoxidative stress, as quantified by HbAC levels and oxidative response in plasma.

摘要

背景

2型糖尿病(T2DM)对ST段抬高型心肌梗死(STEMI)患者血栓成分的作用尚未完全明确。

目的

阐明STEMI糖尿病患者和非糖尿病患者冠状动脉血栓成分的差异,以及这些差异与糖化血红蛋白水平和氧化应激标志物之间的潜在关联。

方法

对25例糖尿病和28例非糖尿病STEMI患者连续进行血栓抽吸术获取的冠状动脉血栓,采用共聚焦显微镜免疫荧光法进行分析。检测外周血中的血浆生物标志物(P-选择素、血管性血友病因子、纤溶酶原激活物抑制剂-1、组织型纤溶酶原激活物、D-二聚体、组织因子途径标志物、纤溶酶和CD34),同时平行检测血浆的氧化能力作为氧化应激的间接指标。

结果

与非糖尿病患者相比,T2DM患者血栓中的纤维蛋白(P=0.03)、P-选择素(P=0.0001)、纤溶酶原激活物抑制剂-1(PAI-1,P=0.03)和血管性血友病因子(vWF,P=0.006)水平更高,血浆组织因子(TF)活性也更高(P=0.01)。TF活性和纤溶酶与糖化血红蛋白水平相关(R=0.71,P=0.0001;R=0.46,P=0.04),且TF与组织因子途径抑制物(TFPI,R=-0.44,P=0.008)和组织型纤溶酶原激活物(tPA,R=-0.48,P=0.003)呈负相关。糖尿病患者血浆的氧化反应更高(通过氢核磁共振波谱法测量,氧化脂质为26.47±6.88%,而非糖尿病患者为22.06±6.96%,P=0.04),这与血栓中纤维蛋白含量增加有关(R=0.76,P=0.01)。

结论

STEMI糖尿病患者的血栓形成性增加,导致其血栓成分与STEMI非糖尿病患者不同。T2DM中增加的血栓形成性与更高的糖氧化应激有关,可通过糖化血红蛋白水平和血浆氧化反应来量化。

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