Department of Medicine and Surgery, Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy.
Department of Interventional Cardiology, Division of Cardiology, Santa Maria University Hospital, Terni, Italy.
Thromb Res. 2022 Aug;216:84-89. doi: 10.1016/j.thromres.2022.06.006. Epub 2022 Jun 22.
Matrix metalloproteinases (MMPs) of atherosclerotic tissue contribute to plaque rupture triggering acute coronary syndromes (ACS). Several MMPs, including MMP-2, are also contained in platelets and released upon activation. An increase in circulating levels of MMP-2 has been reported in patients undergoing percutaneous coronary interventions (PCI), but its time-course and origin remain unclear. Aims of our study were to assess the time-course of MMP-2 release in blood of stable and unstable coronary artery disease patients undergoing PCI and to unravel the possible contribution of platelets to its release.
Peripheral blood samples were drawn immediately before, 4 and 24 h after PCI from patients with ACS (NSTEMI or STEMI, n = 21) or with stable angina (SA, n = 21). Platelet-poor plasma and washed platelet lysates were prepared and stored for subsequent assay of MMP-2 and β-thromboglobulin (β-TG), a platelet-specific protein released upon activation.
Plasma MMP-2 and β-TG increased significantly 4 h after PCI and returned to baseline at 24 h in ACS patients, while they did not change in SA patients. Platelet content of MMP-2 and β-TG decreased significantly 4 h after PCI in patients with ACS, compatible with intravascular platelet activation and release, while they did not change in patients with SA.
PCI triggers the release of MMP-2 in the circulation of ACS patients but not in that of patients with SA. Platelets activated by PCI contribute to the increase of plasma MMP-2 releasing their MMP-2 content. Given that previous mechanicistic studies have shown that MMP-2 may sustain platelet activation and unstabilize downstream-located plaques and in the long term favour restenosis and atherosclerosis progression, these data may encourage the search for therapeutic agents blocking MMP-2 release or activity in ACS.
动脉粥样硬化组织中的基质金属蛋白酶（MMPs）有助于斑块破裂引发急性冠状动脉综合征（ACS）。几种 MMPs，包括 MMP-2，也存在于血小板中，并在激活时释放。已经报道在接受经皮冠状动脉介入治疗（PCI）的患者中循环 MMP-2 水平升高，但其时间过程和来源仍不清楚。我们的研究目的是评估稳定型和不稳定型冠心病患者 PCI 后血液中 MMP-2 释放的时间过程，并阐明血小板对其释放的可能贡献。
从 ACS（NSTEMI 或 STEMI，n=21）或稳定型心绞痛（SA，n=21）患者中立即在 PCI 前、PCI 后 4 和 24 小时采集外周血样本。制备血小板缺乏的血浆和洗涤的血小板裂解物，并储存用于随后测定 MMP-2 和β-血栓球蛋白（β-TG），这是一种在激活时释放的血小板特异性蛋白。
ACS 患者 PCI 后 4 小时血浆 MMP-2 和β-TG 显著升高，24 小时恢复基线，而 SA 患者则没有变化。ACS 患者 PCI 后 4 小时血小板 MMP-2 和β-TG 含量明显下降，提示血管内血小板激活和释放，而 SA 患者则没有变化。
PCI 可触发 ACS 患者循环中 MMP-2 的释放，但不能触发 SA 患者循环中 MMP-2 的释放。PCI 激活的血小板通过释放其 MMP-2 含量促进血浆 MMP-2 的释放。鉴于先前的机械研究表明 MMP-2 可能维持血小板激活并使下游斑块不稳定，并且长期以来有利于再狭窄和动脉粥样硬化进展，这些数据可能鼓励寻找阻断 ACS 中 MMP-2 释放或活性的治疗剂。
