Phosphomimetic endothelial nitric oxide synthase-loaded microbubbles-mediated cardiac shock wave transfection therapy for angiogenesis in the ischemic myocardium

Abstract Background Cardiac shock wave therapy is a potential and effective remedy to promote revascularization in the ischemic myocardium of patients with refractory coronary heart disease (CHD). Although gene holds great promise as treatment for disease, current clinical application hampered by development safe efficient systems local delivery specific tissue or organ. Purpose In this study, we developed an experimental pulsed- focused electrohydraulic system investigated its effectiveness on myocardial angiogenesis hypercholesterolemic rabbit accompanied phosphomimetic endothelial nitric oxide synthase-loaded microbubbles administration, wherein high resolution diagnostic ultrasound adjuncted system, goal increased safety. Methods Briefly, New Zealand white rabbits underwent 2% cholesterol rich diet injury sixteen weeks. Histopathology results showed formation foam cells-rich soft atherosclerotic plaques severe stenosis all rabbits' arteries. Then group extracorporeal pulsed-focused waves (25kV, 0.5Hz, 150 pulses) PESDA (Perfluorocarbon Exposed Sonicated Dextrose Albumin) (100 ml/kg, 2.5x105 bubbles/ml) administration. Results from ultrasonography histopathology significant increase mean value neovessels density compared control (p<0.05). Conclusion Enhanced sonoporation effect therapy, induced inertial collapsed microbubbles, synthase-mediated transfection can cause enhance synthesis VEGF, interleukin8 (IL8), stromal cell- derived factor 1 (SDF1) matrix metalloproteinase 9 (MMP9) secretion arteries, resulting differentiation recruitment progenitor cells (EPCs), promotion improvement cardiac function. Funding Acknowledgement Type funding sources: Public Institution(s). Main source(s): Mehrad Research Lab