AUTHOR=Guo Shengcun , Zhang Shengye , Chen Kui , Chen Xi , Hu Fudong 

TITLE=Effects of diagnostic ultrasound with cRGD-microbubbles on simultaneous detection and treatment of atherosclerotic plaque in ApoE−/− mice

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.946557

DOI=10.3389/fcvm.2022.946557

ISSN=2297-055X

ABSTRACT=Background: Atherosclerotic vulnerable plaque is the leading cause of acute fatal cardiovascular events. Thus, early rapid identification and appropriate treatment of vulnerable plaque can prevent fatal cardiovascular events. However, few noninvasive molecular imaging techniques are currently available for the simultaneous detection and targeted treatment of atherosclerotic plaques. We hypothesized that diagnostic ultrasound (DU) combined with cyclic Arg-Gly-Asp-modified microbubbles (MBR) could provide targeted imaging and dissolution of activated platelets to identify high-risk plaques and improve plaque instability. 
Methods: Three mouse models, apolipoprotein E-deficient mice on a hypercholesterolemic diet (HCD) or normal chow diet and wild-type mice on an HCD were used. The most appropriate ultrasonic mechanical index (MI) was determined based on the expression of GP IIb/IIIa in sham, DU alone and DUMBR-treated groups at MI values of 0.5, 1.5, and 1.9. The video intensity (VI) values, activated platelets and plaque instability were analyzed by ultrasound molecular imaging, scanning electron microscopy and histopathological methods. 
Results: We found that the VI values of ultrasound molecular imaging of MBR were positively correlated with plaque GP IIb/IIIa expression, vulnerability index and necrotic center / fiber cap ratio. Twenty-four hours after treatment at different MIs, compared with those of the other groups, both the VI values and GP IIb/IIIa expression were significantly reduced in MI 1.5 and MI 1.9 DUMBR-treated groups. The plaque vulnerability index and necrotic center / fiber cap ratio were significantly decreased in MI 1.5-treated group, which may be due to targeted dissolution of activated platelets, with a reduction in von Willebrand factor expression. 
Conclusion: DUMBR targeting GP IIb/IIIa receptors can rapidly detect high-risk plaques and simultaneously improve their instability by dissolving activated platelets. This technology may represent a novel approach for the identification and stabilization of high-risk plaques and potentially prevent fatal cardiovascular events.