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血小板在急性冠脉综合征患者的冠状动脉循环中释放基质金属蛋白酶-2:在持续血小板激活中的可能作用。

Platelets release matrix metalloproteinase-2 in the coronary circulation of patients with acute coronary syndromes: possible role in sustained platelet activation.

机构信息

Division of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy.

出版信息

Eur Heart J. 2011 Feb;32(3):316-25. doi: 10.1093/eurheartj/ehq390. Epub 2010 Oct 28.

DOI:10.1093/eurheartj/ehq390
PMID:21036774
Abstract

AIMS

To investigate whether selected matrix metalloproteinases (MMPs) are released in the coronary circulation of patients with acute coronary syndrome (ACS), whether this release is related to platelet activation, and whether it contributes to sustained platelet activation.

METHODS AND RESULTS

Blood from the aorta (Ao) and the coronary sinus (Cs) was obtained from 21 controls (non-cardiac chest pain), 24 stable angina (SA), and 30 ACS patients, before performing percutaneous transluminal coronary angioplasty. Selected MMPs, some platelet activation- and atheroma-related markers, and the platelet activation-potentiating activity of plasma were measured. Total MMP-2, active MMP-2, and MMP-9 were released in the coronary circulation of patients with ACS, but not of those with SA or controls. Similarly, transcoronary gradients of β-thromboglobulin (β-TG) and platelet factor 4, two platelet-specific proteins, and of soluble CD40L and secretory phospholipase A₂ (sPLA₂), markers of inflammation and platelet activation, were higher in ACS patients than in the other groups. In contrast, plasma monocyte chemoattractant protein-1, a platelet-unrelated marker of atherogenesis, was not increased in the Cs compared with Ao in any of the groups. Transcoronary gradients of both β-TG and sPLA₂ correlated with those of total and active MMP-2 in ACS, but not in controls or SA. Plasma from the Cs of ACS patients potentiated platelet activation, an effect suppressed by the specific MMP-2-inhibitor, tissue inhibitor of MMP-2 (TIMP-2).

CONCLUSION

Matrix metalloproteinase-2 is released in the coronary circulation of ACS patients, derives in part from activated platelets, and may contribute to sustained intracoronary platelet activation.

摘要

目的

研究急性冠脉综合征(ACS)患者的冠状动脉循环中是否释放了某些基质金属蛋白酶(MMPs),这种释放是否与血小板激活有关,以及是否有助于持续的血小板激活。

方法和结果

在进行经皮腔内冠状动脉成形术之前,从 21 名对照组(非心脏性胸痛)、24 名稳定性心绞痛(SA)和 30 名 ACS 患者的主动脉(Ao)和冠状窦(Cs)中获得血液。测量了选定的 MMPs、一些与血小板激活和动脉粥样硬化相关的标志物,以及血浆对血小板激活的增强活性。ACS 患者的冠状动脉循环中释放了总 MMP-2、活性 MMP-2 和 MMP-9,但 SA 患者或对照组患者没有。同样,β-血栓球蛋白(β-TG)和血小板因子 4 这两种血小板特异性蛋白,以及可溶性 CD40L 和分泌型 PLA₂(sPLA₂)这两种炎症和血小板激活的标志物,在 ACS 患者中的跨冠状窦梯度也高于其他组。相比之下,Cs 中的单核细胞趋化蛋白-1(一种与血小板无关的动脉粥样硬化形成的标志物)在任何一组中都没有比 Ao 高。ACS 患者的β-TG 和 sPLA₂的跨冠状窦梯度与 ACS 患者总 MMP-2 和活性 MMP-2 的梯度相关,但与对照组或 SA 无关。来自 ACS 患者 Cs 的血浆增强了血小板激活,这种作用被基质金属蛋白酶-2 抑制剂(TIMP-2)抑制。

结论

MMP-2 在 ACS 患者的冠状动脉循环中释放,部分来自激活的血小板,可能有助于持续的冠状动脉内血小板激活。

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