Evidence for a proinflammatory and proteolytic environment in plaques from endarterectomy segments of human carotid arteries
Evidence for a proinflammatory and proteolytic environment in plaques from endarterectomy segments of human carotid arteries
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DOI：
10.1161/01.atv.0000104013.71118.53
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发表时间：
2004-01-01
影响因子：
8.7
通讯作者：
Scanu, AM
中科院分区：
文献类型：
--
作者：
Formato, M;Farina, M;Scanu, AM
基于先前对人类不稳定颈动脉斑块中载脂蛋白(a)，载脂蛋白(a)的观察，我们探讨了在人类动脉粥样硬化的炎症环境中，蛋白质水解事件是否会影响与斑块稳定性问题相关的其他肝脏和局部生成的蛋白质。方法与结果：用缓冲生理盐水（PBS）和6 mol/L盐酸胍（GdHCl）分别提取40个不稳定斑块和24个稳定斑块，鉴定松散和紧密结合产物。在d 1.21 g/mL超离心条件下对提取物进行了研究。在提取物中，白细胞介素(IL)-6、-8和-18的浓度在不稳定斑块中显著升高，并与MMP-2和MMP-9的浓度相关。Western blot结果显示，apoB和apo(a)高度碎片化，主要存在于d 1.21底部，同时含有apoE（10和22 kDa）、decorin、biglycan和versican的片段。不稳定斑块碎裂率更高。在基线血浆中，不稳定斑块和稳定斑块患者的脂质、脂蛋白和il浓度没有差异。结论：在不稳定斑块和较小程度的稳定斑块中，存在促炎和蛋白水解微环境，产生具有潜在病理生物学意义的碎片，需要研究。
Objectives-Based on previous observations on apolipoprotein(a), apo(a), in human unstable carotid plaques, we explored whether in the inflammatory environment of human atheroma, proteolytic events affect other hepatic and topically generated proteins in relation to the issue of plaque stability.Methods and Results-Forty unstable and 24 stable plaques from endarterectomy segments of affected human carotid arteries were extracted with buffered saline (PBS) and then 6 mol/L guanidine-hydrochloride (GdHCl) to identify loosely and tightly bound products, respectively. The extracts were studied before and after ultracentrifugation at d 1.21 g/mL. In the extracts, the concentrations of interleukin (IL)-6, -8, and -18 were significantly higher in the unstable plaques and correlated to those of MMP-2 and MMP-9. By Western blots, both apoB and apo(a) were highly fragmented and mostly present in the d 1.21 bottom that also contained fragments of apoE (10 and 22 kDa), decorin, biglycan, and versican. Fragmentation was higher in the unstable plaques. In baseline plasmas, concentrations of lipids, lipoproteins, and ILs did not differ between patients with unstable and stable plaques.Conclusions-In unstable and to a lesser extent in stable plaques, there is a proinflammatory and proteolytic microenvironment with the generation of fragments with potential pathobiological significance that requires investigation.