Abstract 17823: Detection of Platelet-rich Thrombus on Atherosclerotic Plaque by Ultrasound Molecular Imaging

Abstract

Background: The role of platelet-rich thrombosis in accelerating plaque progression and stimulating atherosclerotic plaque instability is well established. Previous studies have demonstrated that the platelet-rich thrombus can be detected in the setting of acute endothelial inflammation without atherosclerosis by ultrasound molecular imaging (UMI). However, it has not been defined in atherosclerotic model. We, therefore, hypothesized that microbubbles targeted to activated platelet with contrast-enhanced ultrasound (CEU) could detect the platelet-rich thrombus on atherosclerosis and identify vulnerable plaques.

Methods: The cyclic RGD peptide (MB_RGD) or nonspecific peptide (MB_CON) was attached covalently to lipid-microbubbles via thiol-maleimide coupling. Flow chamber studies were performed to assess the specific attachment of both agents to glycoprotein αIIbβ3. 48 wild-type and 48 apolipoprotein E-deficient (Apoe^-/-) mice were equally divided into chow and hypercholesterolemic (western) diet. CEU of the abdominal aorta was carried out after the mice consumed a chow or western diet for 4,8,12,16 weeks starting at 6 weeks of age (n=6 per group); then animals were sacrificed. The aortas were harvested for histological and immunohistochemical examinations.

Results: The attachment of MB_RGD to the glycoprotein αIIbβ3 was showed a good affinity, but not that of MB_CON. As expected, the platelet-rich thrombosis, the GPIIb/IIIa receptor expression of the thrombus, the vulnerability index and the ratio of (necrotic core)/(fibrous cap) (NC/FC) were exhibited a descending order of Apoe^-/- + western > Apoe^-/- + chow > wild-type + western > wild-type + chow (P<0.05). Interestingly, there were good relations between video intensity of the MB_RGD at 10 minutes after microbubbles injection and the expression of GPIIb/IIIa receptor, the vulnerability index and the ratio of NC/FC on atherosclerotic plaque in all mice (r=0.86, 0.78 and 0.72, respectively, P<0.01).

Conclusions: The platelet-rich thrombus on atherosclerotic plaque can be detected by UMI with microbubbles targeted to glycoprotein GPIIb/IIIa receptor, and thus predicting atherosclerotic plaque instability.