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一种弥散斑块微钙化的模式可识别出急性心肌梗死患者中具有高炎症负担的斑块亚群。

A pattern of disperse plaque microcalcifications identifies a subset of plaques with high inflammatory burden in patients with acute myocardial infarction.

机构信息

Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

出版信息

Atherosclerosis. 2011 Sep;218(1):83-9. doi: 10.1016/j.atherosclerosis.2011.04.032. Epub 2011 May 5.

Abstract

AIMS

Inflammation plays a crucial role in plaque vulnerability. Calcifications can be detected by means of in vivo imaging techniques. The study purpose is to assess a potential association between tissue localization of calcifications and the inflammatory biomarkers, C-reactive protein (CRP), osteopontin and lipoprotein-associated phospholipase A2 (Lp-PLA2), in plaque tissue of patients with acute myocardial infarction (AMI).

METHODS AND RESULTS

Thrombectomy materials obtained from patients with electrocardiographically documented ST-segment elevation type of AMI (STEMI) were histologically screened for presence of thrombus, plaque tissues and calcifications. Size of calcifications was measured morphometrically, and their colocalization with the inflammatory biomarkers macrophages, CRP, osteopontin and Lp-PLA2 was assessed with immunostaining. A total of 171 samples containing plaque tissues were obtained from 562 thrombectomy procedures. Calcifications were observed in 67 (39%) plaque fragments, with diameters ranging from 4 to 170 μm. Plaque tissues with calcifications contained more frequently extracellular CRP and intracellular CRP in macrophages than those without calcifications (85%, 59% vs. 64%, 32%, P=0.012 and 0.005 respectively). Similar results were obtained with osteopontin immunostaining (98%, 76% vs. 56%, 40%; P<0.001 both). Furthermore, samples with calcifications were immunostained for CRP more intensely than those without calcifications (P=0.001). Finally, 96% of the plaque tissues stained positively for Lp-PLA2, but there was no association with presence of microcalcifications.

CONCLUSIONS

A pattern of disperse microcalcifications is positively associated with presence of the inflammatory biomarkers macrophages, CRP and osteopontin in thrombectomy materials of STEMI patients. Based on these findings, we speculate that such microcalcifications could have the potential to serve as a surrogate marker for plaques with high inflammatory burden.

摘要

目的

炎症在斑块易损性中起着至关重要的作用。可以通过体内成像技术检测钙化。本研究旨在评估急性心肌梗死(AMI)患者斑块组织中钙化的组织定位与炎症生物标志物 C 反应蛋白(CRP)、骨桥蛋白和脂蛋白相关磷脂酶 A2(Lp-PLA2)之间的潜在相关性。

方法和结果

从经心电图证实的 ST 段抬高型急性心肌梗死(STEMI)患者的血栓切除术材料中,通过组织学筛选出血栓、斑块组织和钙化。通过形态计量学测量钙化的大小,并通过免疫染色评估其与炎症标志物巨噬细胞、CRP、骨桥蛋白和 Lp-PLA2 的共定位。从 562 次血栓切除术获得了 171 个含有斑块组织的样本。在 67(39%)个斑块碎片中观察到钙化,直径范围为 4 至 170μm。与无钙化的斑块组织相比,含有钙化的斑块组织中巨噬细胞胞外 CRP 和胞内 CRP 的含量更高(85%,59%比 64%,32%,P=0.012 和 0.005)。骨桥蛋白免疫染色也得到了类似的结果(98%,76%比 56%,40%;P<0.001)。此外,与无钙化的斑块组织相比,含有钙化的斑块组织对 CRP 的免疫染色强度更高(P=0.001)。最后,96%的斑块组织对 Lp-PLA2 呈阳性染色,但与微钙化的存在无关。

结论

STEMI 患者血栓切除术材料中弥散性微钙化的存在与炎症标志物巨噬细胞、CRP 和骨桥蛋白呈正相关。基于这些发现,我们推测这种微钙化可能有潜力作为炎症负荷高的斑块的替代标志物。

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