Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China.
PLoS One. 2012;7(3):e33523. doi: 10.1371/journal.pone.0033523. Epub 2012 Mar 20.
Angiotensin II (ANG II) promotes vascular inflammation and induces abdominal aortic aneurysm (AAA) in hyperlipidemic apolipoprotein E knock-out (apoE(-/-)) mice. The aim of the present study was to detect macrophage activities in an ANG II-induced early-stage AAA model using superparamagnetic iron oxide (SPIO) as a marker.
METHODOLOGY/PRINCIPAL FINDINGS: Twenty-six male apoE(-/-) mice received saline or ANG II (1000 or 500 ng/kg/min) infusion for 14 days. All animals underwent MRI scanning following administration of SPIO with the exception of three mice in the 1000 ng ANG II group, which were scanned without SPIO administration. MR imaging was performed using black-blood T2 to proton density -weighted multi-spin multi-echo sequence. In vivo MRI measurement of SPIO uptake and abdominal aortic diameter were obtained. Prussian blue, CD68,α-SMC and MAC3 immunohistological stains were used for the detection of SPIO, macrophages and smooth muscle cells. ANG II infusion with 1000 ng/kg/min induced AAA in all of the apoE(-/-) mice. ANG II infusion exhibited significantly higher degrees of SPIO uptake, which was detected using MRI as a distinct loss of signal intensity. The contrast-to-noise ratio value decreased in proportion to an increase in the number of iron-laden macrophages in the aneurysm. The aneurysmal vessel wall in both groups of ANG II treated mice contained more iron-positive macrophages than saline-treated mice. However, the presence of cells capable of phagocytosing haemosiderin in mural thrombi also induced low-signal-intensities via MRI imaging.
CONCLUSIONS/SIGNIFICANCE: SPIO is taken up by macrophages in the shoulder and the outer layer of AAA. This alters the MRI signaling properties and can be used in imaging inflammation associated with AAA. It is important to compare images of the aorta before and after SPIO injection.
血管紧张素 II（ANG II）可促进血管炎症，并在高脂血症载脂蛋白 E 敲除（apoE（-/-））小鼠中诱导腹主动脉瘤（AAA）。本研究的目的是使用超顺磁氧化铁（SPIO）作为标志物，检测 ANG II 诱导的早期 AAA 模型中的巨噬细胞活性。
方法/主要发现：26 只雄性 apoE（-/-）小鼠接受盐水或 ANG II（1000 或 500ng/kg/min）输注 14 天。除了 ANG II 1000ng 组的三只小鼠未进行 SPIO 给药而直接进行 MRI 扫描外，所有动物均在 SPIO 给药后进行 MRI 扫描。MR 成像采用黑血 T2 质子密度加权多自旋多回波序列进行。通过体内 MRI 测量 SPIO 摄取和腹主动脉直径。普鲁士蓝、CD68、α-SMC 和 MAC3 免疫组化染色用于检测 SPIO、巨噬细胞和平滑肌细胞。ANG II 输注 1000ng/kg/min 可诱导所有 apoE（-/-）小鼠发生 AAA。ANG II 输注导致 SPIO 摄取显著增加，MRI 检测到信号强度明显降低。与动脉瘤中含铁巨噬细胞数量增加成比例的，是对比噪声比（CNR）值降低。两组 ANG II 处理的小鼠的动脉瘤血管壁中含有更多的铁阳性巨噬细胞，而非盐水处理的小鼠。然而，血管壁中层血栓中的吞噬含铁血黄素的细胞也通过 MRI 成像引起低信号强度。
结论/意义：SPIO 被 AAA 的肩部和外层的巨噬细胞摄取。这改变了 MRI 的信号特性，并可用于成像与 AAA 相关的炎症。在 SPIO 注射前后比较主动脉图像非常重要。
