Functional Activity and Endothelial-Lining Integrity of Ex Vivo Arteries Exposed to Ultrasound-Mediated Microbubble Destruction |
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| Institution: | 2. Universidad de Monterrey, San Pedro Garza García, México;2. Department of Medical Imaging, St. Francis Xavier Cabrini Hospital, Malvern, Victoria, Australia;3. Department of Medical Imaging, Mercy Hospital for Women, Heidelberg, Victoria, Australia;4. Monash Newborn, Monash Medical Centre, Clayton, Victoria, Australia;5. The Ritchie Centre, Hudson''s Institute of Medical Research, Melbourne, Victoria, Australia;11. Department of Medical Imaging, Townsville General Hospital, Douglas, Queensland, Australia;2. Chongqing Key Laboratory of Biomedical Chongqing Medical University, Chongqing, China;2. Cardiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA;3. Cardiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA;2. National-regional Key Technology Engineering Laboratory for Medical Ultrasound, Shenzhen, Guangdong, China;2. Department of Biology, Concordia University, Montreal, Quebec, Canada;3. Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;4. Department of Cell Biology, Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;5. Pittsburgh Heart and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;2. Regenerative Bioscience Center, University of Georgia, Athens, Georgia, USA;3. Schlegel Research Institute for Aging, University of Waterloo, Waterloo, ON, Canada |
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| Abstract: | Ultrasound-mediated microbubble destruction (UMMD) is a promising strategy to improve local drug delivery in specific tissues. However, acoustic cavitation can lead to harmful bioeffects in endothelial cells. We investigated the side effects of UMMD treatment on vascular function (contraction and relaxation) and endothelium integrity of ex vivo Wistar rat arteries. We used an isolated organ system to evaluate vascular responses and confocal microscopy to quantify the integrity and viability of endothelial cells. The arteries were exposed for 1–3 min to ultrasound at a 100 Hz pulse-repetition frequency, 0.5 MPa acoustic pressure, 50% duty cycle and 1%–5% v/v microbubbles. The vascular contractile response was not affected. The acetylcholine-dependent maximal relaxation response was reduced from 78% (control) to 60% after 3 min of ultrasound exposure. In arteries treated simultaneously with 1 min of ultrasound exposure and 1%, 2%, 3% or 5% microbubble concentration, vascular relaxation was reduced by 19%, 58%, 80% or 93%, respectively, compared with the control arteries. Fluorescent labeling revealed that apoptotic death, detachment of endothelial cells and reduced nitric oxide synthase phosphorylation are involved in relaxation impairment. We demonstrated that UMMD can be a safe technology if the correct ultrasound and microbubble parameters are applied. Furthermore, we found that tissue-function evaluation combined with cellular analysis can be useful to study ultrasound–microbubble–tissue interactions in the optimization of targeted endothelial drug delivery. |
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