Theranostics 2015; 5(4):418-430. doi:10.7150/thno.10020

Research Paper

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

Shengcun Guo, Shuxin Shen, Junfen Wang, He Wang, Meiyu Li, Ying Liu, Fanfan Hou, Yulin Liao, Jianping Bin

State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Abstract

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 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.

Keywords: Atherosclerosis, Microbubbles, Molecular imaging, Platelets, Glycoprotein IIb/IIIa

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How to cite this article:
Guo S, Shen S, Wang J, Wang H, Li M, Liu Y, Hou F, Liao Y, Bin J. Detection of High-Risk Atherosclerotic Plaques with Ultrasound Molecular Imaging of Glycoprotein IIb/IIIa Receptor on Activated Platelets. Theranostics 2015; 5(4):418-430. doi:10.7150/thno.10020. Available from http://www.thno.org/v05p0418.htm