Background: 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 stroke and cardiovascular disease. Foam cells are generated by uncontrolled uptake of modified LDL, especially oxidized LDL (oxLDL).

Aims: In this study, we developed an experimental transfection therapy protocol using focused- low­ level confocal dual -pulse electrohydraulic shock waves and investigated its effectiveness on macrophage foam cells density reduction, wherein diagnostic B- mode ultrasound is combined with shock wave therapy system, with a goal of increased safety.

Methods: Briefly, Golden Syrian hamsters underwent primary balloon dilatation injury at the abdominal aorta followed by a 1.5% cholesterol-rich diet injury for three weeks. Histopathology results showed the formation of early stage atherosclerosis in all of the hamsters´ arteries. Then animals’ arteries in the treatment group at the lesion region, treated using Phosphomimetic Endothelial Nitric Oxide Synthase – loaded microbubbles- mediated transfection therapy using
B-mode ultrasound- guided focused- Low­ level confocal dual- ­pulse electrohydraulic shock waves (V= 15 Kv, F= 2Hz, Impulses= 50 and V= 10 Kv, F= 0.5Hz, Impulses= 150). 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 early atherosclerotic lesion in the treatment group compared with the control group (p< 0.05).

Conclusions: Enhanced sonoporation therapy effect of shock waves, induced by inertial cavitation effect of microbubbles accompanied by Phosphomimetic Endothelial Nitric Oxide Synthase – loaded microbubbles administration can cause to reduce the foam cells density within the lesion and significantly enhance of protein expression and nitric oxide synthesiss. This protocol is a feasible and efficient method for the vascular early stage atherosclerosis regression.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/effect-of-phosphomimetic-endothelial-nitric-oxide-synthase-loaded-microbubbles-mediated-transfection-therapy-using-b-mode-ultrasound-guided-focused-low-level-confocal-dual-pulse-electrohydra/