title: Detection of high-risk atherosclerotic plaques with ultrasound molecular imaging of glycoprotein IIb/IIIa receptor on activated platelets.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Shengcun
authors.initials: S
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Shuxin
authors.initials: S
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Junfen
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Fanfan
authors.initials: F
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Bin
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001792:Blood Platelets / Q000737:chemistry*; D004195:Disease Models, Animal; D039661:Integrin beta3 / Q000032:analysis*; D008810:Mice, Inbred C57BL; D045423:Microbubbles; D057054:Molecular Imaging / Q000379:methods*; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D040201:Platelet Membrane Glycoprotein IIb / Q000032:analysis*; D014463:Ultrasonography / Q000379:methods*
chemical_list: D015415:Biomarkers; D039661:Integrin beta3; D040201:Platelet Membrane Glycoprotein IIb
keywords: Atherosclerosis; Glycoprotein IIb/IIIa; Microbubbles; Molecular imaging; Platelets