Sonodynamic Therapy of Early Stage Atherosclerosis Using Pulsed Low: Intensity Focused Ultrasound Accompanied by Protoporphyrin ІX-Loaded Microbubbles Administration

Introduction: Most acute cardiovascular events result from the rupture of an atherosclerotic plaque, and macrophage- derived foam cells play a crucial role in the progression.
Aim: In this study, we developed an experimental pulsed low- intensity focused ultrasound and investigated its effectiveness on foam cells reduction in the early stage atherosclerosis accompanied by protoporphyrin ІX-loaded microbubbles administration.
Methods: Briefly, New Zealand white rabbits underwent balloon dilatation injury at the abdominal aorta (approximately 2 cm superior to the iliac bifurcation) before being fed a 1.5% cholesterol- rich diet. After two weeks, the histopathology results showed macrophages foam cell-rich fatty streaks formation, resulting in vessel wall thickening. Then treatment group underwent sonodynamic therapy with pulsed low- intensity focused ultrasound (F= 1MHz, DF= 50%, I= 3W/cm2) accompanied by protoporphyrin- ІX (50 mg/kg)- loaded PESDA (Perfluorocarbon-Exposed Sonicated Dextrose Albumin) microbubbles (100 ml/kg, 2- 5 ×105 bubbles/ml) administration.
Results: Color Doppler, B-mode ultrasound and histopathology results showed a significant reduction in the mean value for blood mean velocity, macrophage- derived foam cell fatty streaks, wall mean thickness and a significant increase in the mean value for blood volume flow in the treatment group compared with the other groups (P<0.05).
Conclusion: Inertial cavitation effect of destructed PESDA microbubbles- induced by pulsed low- intensity focused ultrasound, can cause to increase the localized cytotoxic effect of protoporphyrin- ІX resulting in the macrophages foam cells reduction. Protoporphyrin ІX-mediated sonodynamic therapy using pulsed low- intensity focused ultrasound may be a potential treatment for the early stage atherosclerosis.