PROTOPORPHYRIN IX- LOADED MICROBUBBLES- MEDIATED SONODYNAMIC THERAPY REDUCE FOAM CELLS IN THE EARLY ATHEROSCLEROSIS

Aim: In atherosclerosis, local inflammation and associated macrophage activity can lead to foam cell- rich plaque formation, which results to plaque rupture and thrombosis, making inflammation an important therapeutic target in cardiovascular disease. In this study,we developed an experimental electrohydraulic shock wave generator system (0- 20 Kv, 0.1- 5 Hz), and investigated its effectiveness on macrophage foam cells density reduction. Methods: Briefly, New Zealand white rabbits' abdominal aorta (approximately 2 cm superior to the iliac bifurcation) underwent primary balloon dilatation injury followed by a 1.5% cholesterol-rich diet injury for four weeks. Histopathology results showed foam cells- rich atherosclerotic plaque formation in all of the rabbits' artery. Then, abdominal aorta of the treatment group at lesion region, treated using extracorporeal low- level (8Kv) focused- electrohydraulic shock waves accompanied by protoporphyrin IX- loaded PESDA (Perflurocarbon- Exposed Sonicated Dextrose Albumin) microbubbles (100ml/kg, 2-5 ?105 bubbles/ml) administration. Foam cells density were evaluated in the treatment group compared with the control group using B-mode ultrasonography and histology. Results: Results from B-mode ultrasonography and histopathology showed a significant reduction in the mean value for foam cells density within the lesion in the treatment group compared with the control group (p < 0.05). Conclusions: PESDA microbubbles preferentially adhere to inflammatory endothelial. Inertial cavitation effect of PESDA microbubbles- induced by shock waves cause to enhance anti- inflammatory effect of protoporphyrin IX. Furthermore shock waves reduce macrophage foam cells via ERKmediated increase of ABCA-1 and ABCG-1 mediating lipid efflux and promotes macrophage migration which may induce macrophage egress from atherosclerotic lesion.