Guo Shengcun, Shen Shuxin, Wang Junfen, Wang He, Li Meiyu, Liu Ying, Hou Fanfan, Liao Yulin, Bin Jianping
State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Theranostics. 2015 Feb 5;5(4):418-30. doi: 10.7150/thno.10020. eCollection 2015.
Ultrasound molecular imaging (UMI) of glycoprotein (GP) IIb/IIIa receptor on activated platelets offers a unique means of identifying high-risk atherosclerosis. We hypothesized that contrast-enhanced ultrasound with microbubbles (MBs) targeted to GP IIb/IIIa could be used to detect and quantify activated platelets on the surface of advanced plaques.
A mouse model of advanced atherosclerosis was generated by maintaining apolipoprotein E-deficient (ApoE(-/-)) mice on a hypercholesterolemic diet (HCD). The three other experimental groups consisted of ApoE(-/-) and wild-type (C57BL/6) mice fed a normal chow diet and C57BL/6 mice on an HCD diet. Plaque formation was confirmed by histological and immunohistochemical methods using light, fluorescence, and electron microscopy. Mice were injected with a lipid MB-conjugated cyclic Arg-Gly-Asp peptide or nonspecific control peptide, and the abdominal aorta was examined by UMI. The accumulation of GP IIb/IIIa and activated platelets on the surface of atherosclerotic plaques was highest in the ApoE(-/-)+HCD group, followed by ApoE(-/-)+chow, C57BL/6+HCD, and C57BL/6+chow groups (P<0.05). Notably, GP IIb/IIIa expression was associated with the vulnerability index and necrotic center/fiber cap ratio (P<0.05), and contrast video intensity from adhered cyclic Arg-Gly-Asp-modified MBs (MB-cRGDs) was correlated with GP IIb/IIIa expression on the plaque surface (P<0.05).
GP IIb/IIIa of activated platelets on the atherosclerotic endothelium is a biomarker for high-risk plaques that can be quantified by UMI using MB-cRGDs, providing a noninvasive means for detecting high-risk plaques and preventing acute cardiovascular events.
对活化血小板上的糖蛋白（GP）IIb/IIIa受体进行超声分子成像（UMI）为识别高危动脉粥样硬化提供了一种独特方法。我们推测，靶向GP IIb/IIIa的微泡（MBs）增强超声可用于检测和量化晚期斑块表面的活化血小板。
通过给载脂蛋白E缺陷（ApoE(-/-)）小鼠喂食高胆固醇饮食（HCD）建立晚期动脉粥样硬化小鼠模型。其他三个实验组包括喂食正常饲料的ApoE(-/-)和野生型（C57BL/6）小鼠以及喂食HCD饮食的C57BL/6小鼠。使用光镜、荧光显微镜和电子显微镜通过组织学和免疫组织化学方法确认斑块形成。给小鼠注射脂质MB偶联的环Arg-Gly-Asp肽或非特异性对照肽，并用UMI检查腹主动脉。动脉粥样硬化斑块表面GP IIb/IIIa和活化血小板的积聚在ApoE(-/-)+HCD组中最高，其次是ApoE(-/-)+正常饲料组、C57BL/6+HCD组和C57BL/6+正常饲料组（P<0.05）。值得注意的是，GP IIb/IIIa表达与易损性指数和坏死中心/纤维帽比值相关（P<0.05），并且来自黏附的环Arg-Gly-Asp修饰的MBs（MB-cRGDs）的对比 video强度与斑块表面的GP IIb/IIIa表达相关（P<0.05）。
动脉粥样硬化内皮上活化血小板的GP IIb/IIIa是高危斑块的生物标志物，可通过使用MB-cRGDs的UMI进行量化，为检测高危斑块和预防急性心血管事件提供了一种非侵入性方法。
