Ultrasound-guided imaging of junctional adhesion molecule-A-targeted microbubbles identifies vulnerable plaque in rabbits
Ultrasound-guided imaging of junctional adhesion molecule-A-targeted microbubbles identifies vulnerable plaque in rabbits
复制标题
超声引导下连接粘附分子 A 靶向微泡成像可识别兔子的易损斑块
DOI：
10.1016/j.biomaterials.2016.03.049
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发表时间：
2016-07-01
期刊：
影响因子：
14
通讯作者：
Duan, Yun-You
中科院分区：
文献类型：
--
作者：
Zhang, Ya-Jun;Bai, Dan-Na;Duan, Yun-You
近年来，通过对分子特征进行成像来识别易损动脉粥样硬化斑块的研究备受关注，其中特定标志物的验证是关键步骤。连接黏附分子A（JAM - A）是一种连接膜蛋白，参与斑块形成，但它能否作为易损斑块的标志物尚不明确。分别通过高胆固醇饮食联合或不联合颈动脉部分结扎的方式，在兔体内构建易损斑块和稳定斑块模型。结果发现，易损斑块中JAM - A的表达显著高于稳定斑块。此外，JAM - A不仅在内皮细胞中表达，在CD68阳性区域也大量表达。接下来，通过将生物素化抗体与链霉亲和素修饰的微泡结合，制备了JAM - A抗体偶联微泡（MBJAM_A）或对照IgG偶联微泡（MBC），并利用超声造影（CEUS）进行成像观察。在易损斑块中，MBJAM_A的信号强度显著增强且持续时间延长，部分MBJAM_A与CD68阳性巨噬细胞共定位。另外，细胞模型显示MBJAM_A能够被活化的巨噬细胞吞噬。综上所述，我们发现JAM - A表达增加可作为易损斑块的标志物，靶向超声造影有可能成为一种新型的无创性易损斑块分子成像方法。（C）2016爱思唯尔有限公司版权所有。
Identification of vulnerable atherosclerotic plaques by imaging the molecular characteristics is intensively studied recently, in which verification of specific markers is the critical step. JAM-A, a junctional membrane protein, is involved in the plaque formation, while it is unknown whether it can serve as a marker for vulnerable plaques. Vulnerable and stable plaques were created in rabbits with high cholesterol diet with or without partial ligation of carotid artery respectively. Significant higher JAM-A expression was found in vulnerable plaques than that in stable plaques. Furthermore, JAM-A was not only expressed in the endothelium, but also abundantly expressed in CD68-positive area. Next, JAM-A antibody conjugated microbubbles (MBJAM_A) or control IgG-conjugated microbubbles (MBC) were developed by conjugating the biotinylated antibodies to the streptavidin modified microbubbles, and visualization by contrast-enhance ultrasound (CEUS). Signal intensity of MBJAM_A was substantially enhanced and prolonged in the vulnerable plaque and some of the MBJAM_A was found colocalized with CD68 positive macrophages. In addition, cell model revealed that MBJAM_A were able to be phagocytized by activated macrophages. Taken together, we have found that increase of JAM-A serves as a marker for vulnerable plaques and targeted CEUS would be possibly a novel non-invasive molecular imaging method for plaque vulnerability. (C) 2016 Elsevier Ltd. All rights reserved.