Targeted microbubble cavitation has no therapeutic effect on atherosclerotic plaques of the aorta in diabetic ApoE^-/- mice

Aim:

Diabetes mellitus (DM) increases plaque instability via inflammation. Ultrasound-activated microbubble cavitation has previously reduced intra-plaque neovascularisation in non-DM models. Here we studied how ultrasound-activated microbubbles targeted against intercellular adhesion molecule-1 and CD90 affect atherosclerotic plaques in a DM model. 

Methods:

DM was induced in C57BL/6 ApoE ^-/- mice via streptozotocin injection. Sixteen weeks later, either 5 × 10⁷ targeted microbubbles or the vehicle was applied, followed by 1 min of 1 MHz pulsed thoracic ultrasound with 100 kPa peak negative acoustic pressure and a 1 kHz pulse repetition frequency (10% duty cycle). Aortic root plaque characteristics were examined via (immuno)histochemical analyses 4 wk post-treatment. Circulating monocyte subsets were assessed with flow cytometry in blood samples obtained within 3 d pre- and post-treatment, and 4 wk post-treatment. 

Results:

Targeted microbubble cavitation did not significantly affect atherosclerotic plaque size or intra-plaque inflammation, despite a positive trend in intra-plaque CD45⁺ leukocytes and Ly6G⁺ neutrophils. Ultrasound-activated microbubble cavitation significantly increased the percentage of inflammatory classical monocytes within 3 d post-treatment. 

Conclusions:

Targeted microbubble cavitation induced a significant but temporary increase in circulating pro-inflammatory monocytes under mild exposure conditions in diabetic ApoE ^-/- mice without atherosclerotic plaque alterations.