Detection of High-Risk Atherosclerotic Plaques with Ultrasound Molecular Imaging of Glycoprotein IIb/IIIa Receptor on Activated Platelets

作者：Shengcun Guo, Shuxin Shen, Junfen Wang, He Wang, Meiyu Li, Ying Liu, Fanfan Hou, Yulin Liao, Jianping Bin · 发表于：Theranostics · 年份：2015 · DOI：10.7150/thno.10020 · 被引用次数：40 · 研究领域：Coronary Interventions and Diagnostics、Ultrasound and Hyperthermia Applications、Platelet Disorders and Treatments

OBJECTIVE: 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. METHODS AND RESULTS: 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). CONCLUSION: GP IIb/IIIa of activated platel...