Role of Intracellular Calcium and Reactive Oxygen Species in Microbubble-Mediated Alterations of Endothelial Layer Permeability

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Abstract

Drugs will be delivered to diseased tissue more efficiently if the vascular endothelial permeability is increased. Ultrasound in combination with an ultrasound contrast agent is known to increase the permeability of the endothelial layer, but the mechanism is not known. The goal of this study was to elucidate whether intracellular calcium ions, [Ca2+](i), and reactive oxygen species (ROS) are part of the mechanism that leads to an increased endothelial layer permeability following ultrasound and microbubble treatment. Human umbilical vein endothelial cells (HUVECs) treated for 2 min with ultrasound-activated microbubbles (1 MHz, 210 kPa, 10 000 cycles, 20 Hz repetition rate) had an increased permeability that lasted up to 12 h. Recovery of permeability after 2 h was only found when HUVECs were preincubated with the [Ca2+](i) chelator BAPTA-AM or the antioxidant butylated hydroxytoluene (BHT). This suggests that both [Ca2+](i) and ROS play an important role in the mechanism of increased permeability following ultrasound in combination with microbubble treatment.
Original languageUndefined/Unknown
Pages (from-to)1811-1815
Number of pages5
JournalIEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control
Volume60
Issue number9
DOIs
Publication statusPublished - 2013

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