Sun Ruiying, Tian Jie, Zhang Jun, Wang Liping, Guo Jing, Liu Yani
Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
PLoS One. 2017 Oct 5;12(10):e0186155. doi: 10.1371/journal.pone.0186155. eCollection 2017.
The upregulation of vascular cell adhesion molecule-1(VCAM-1) on vascular endothelium plays a great role in the progression of atherosclerosis (AS). In this study, ultrasound molecular imaging was performed to monitor the inflammation injuries in the onset and progression of atherosclerosis with microbubbles targeted to VCAM-1.
Mice deficient for the apolipoprotein E (ApoE-/-mice) with high-cholesterol diet were studied as an age-dependent model of atherosclerosis. At 8, 16, 24, and 32 weeks of age, contrast enhanced ultrasound (CEU) molecular imaging of proximal ascending aorta was performed with microbubbles targeted to VCAM-1. Plaque size, monocytes infiltration and the expression of VCAM-1 in the proximal ascending aorta were assessed by histology and western blot analysis, separately.
In ApoE-/- mice, molecular imaging for VCAM-1 detected selective signal enhancement (P<0.01 versus non-targeted microbubbles) at all ages of ApoE-/- mice. Moreover, signals from targeted microbubbles increased from 8wks to 32wks age (P<0.05 for trend) in ApoE-/- mice, indicating the upregulation of VCAM-1 with the progression of atherosclerosis. Consistent with CEU imaging results, both western blot analysis and immunohistochemistry revealed the expression of VCAM-1 and monocytes infiltration were age-dependent in ApoE-/- mice.
CEU molecular imaging can be used to noninvasively detect the VCAM-1 expression on the endothelium in the progression of atherosclerosis. By investigating specific molecular biomarkers, it could help to monitor the inflammation and the progression of AS, which may in some extent contribute to the prediction of vulnerable plaque.
血管内皮上血管细胞黏附分子-1（VCAM-1）的上调在动脉粥样硬化（AS）进展中起重要作用。本研究采用超声分子成像技术，利用靶向VCAM-1的微泡监测动脉粥样硬化发生和进展过程中的炎症损伤。
以高脂饮食喂养的载脂蛋白E缺陷小鼠（ApoE-/-小鼠）作为动脉粥样硬化的年龄依赖性模型。在8、16、24和32周龄时，用靶向VCAM-1的微泡对升主动脉近端进行超声造影（CEU）分子成像。分别通过组织学和蛋白质印迹分析评估升主动脉近端的斑块大小、单核细胞浸润及VCAM-1的表达。
在ApoE-/-小鼠中，针对VCAM-1的分子成像在各年龄阶段均检测到选择性信号增强（与非靶向微泡相比，P<0.01）。此外，在ApoE-/-小鼠中，靶向微泡的信号从8周龄到32周龄增加（趋势P<0.05），表明随着动脉粥样硬化的进展VCAM-1上调。与CEU成像结果一致，蛋白质印迹分析和免疫组织化学均显示ApoE-/-小鼠中VCAM-1的表达和单核细胞浸润与年龄相关。
CEU分子成像可用于无创检测动脉粥样硬化进展过程中内皮上VCAM-1的表达。通过研究特定分子生物标志物，有助于监测AS的炎症和进展，这在一定程度上可能有助于预测易损斑块。
