The role of Ca2+ in ultrasound-elicited bioeffects: progress, perspectives and prospects

Hassan, Mona M.; Campbell, Paul A.; Kondo, Takashi

doi:10.1016/j.drudis.2010.08.005

Cited by 80 publications

(63 citation statements)

References 100 publications

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“…Clearly the influx of Ca 2+ plays a pivotal role in the ultrasound enhanced endocytotic activity [134]. As already extensively discussed, higher shear forces can result in a physical disruption of the cell membrane which will also lead to elevated intracellular Ca 2+ levels due to a concentration driven passive diffusion of Ca…”

Section: +mentioning

confidence: 97%

“…In contrast, stable microbubbles oscillations will create only smaller cell membrane disruptions (nm scale) and might be as well removed from the cell membrane via endocytosis. Since the Ca 2+ influx is known to be a dominant trigger for cell repair, it is very likely that intracellular Ca 2+ concentrations will determine which repair mechanism becomes active or whether cellular apoptosis proceeds when the Ca 2+ influx exceeds a certain threshold [134,143]. Recent insights from Idone and colleagues suggest that both mechanism are taking place in membrane resealing [144].…”

Section: +mentioning

confidence: 99%

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Understanding ultrasound induced sonoporation: Definitions and underlying mechanisms

Lentacker

Cock

Deckers

et al. 2014

Advanced Drug Delivery Reviews

622

592

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In the past two decades, research has underlined the potential of ultrasound and microbubbles to enhance drug delivery. However, there is less consensus on the biophysical and biological mechanisms leading to this enhanced delivery. Sonoporation, i.e. the formation of temporary pores in the cell membrane, as well as enhanced endocytosis is reported. Because of the variety of ultrasound settings used -and corresponding microbubble behavior, a clear overview is missing. Therefore, in this review, the mechanisms contributing to sonoporation are categorized according to three ultrasound settings: i) low intensity ultrasound leading to stable cavitation of microbubbles, ii) high intensity ultrasound leading to inertial cavitation with microbubble collapse, and iii) ultrasound application in the absence of microbubbles. Using low intensity ultrasound, the endocytotic uptake of several drugs could be stimulated, while short but intense ultrasound pulses can be applied to induce pore formation and the direct cytoplasmic uptake of drugs. Ultrasound intensities may be adapted to create pore sizes correlating with drug size. Small molecules are able to diffuse passively through small pores created by low intensity ultrasound treatment. However, delivery of larger drugs such as nanoparticles and gene complexes, will require higher ultrasound intensities in order to allow direct cytoplasmic entry.2

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Section: +mentioning

confidence: 97%

Section: +mentioning

confidence: 99%

Understanding ultrasound induced sonoporation: Definitions and underlying mechanisms

Lentacker

Cock

Deckers

et al. 2014

Advanced Drug Delivery Reviews

622

592

View full text Add to dashboard Cite

show abstract

“…Ultrasound has been reported to induce sonoporation and subsequent influx of calcium ion, which was correlated to the LIPUS-induced bioeffects in cultured cells. 33 Thus, it is possible that the LIPUS exerts several biological effects through alteration of intracellular Ca 2+ levels. This point remains to be examined in future studies.…”

Section: Biological Effects Of Lipus Other Than Angiogenesismentioning

confidence: 99%

Low-Intensity Pulsed Ultrasound Enhances Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Mouse Model of Acute Myocardial Infarction

Shindo

Ito

Ogata

et al. 2016

ATVB

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Objective-Left ventricular (LV) remodeling after acute myocardial infarction still remains an important issue in cardiovascular medicine. We have recently demonstrated that low-intensity pulsed ultrasound (LIPUS) therapy improves myocardial ischemia in a pig model of chronic myocardial ischemia through enhanced myocardial angiogenesis. In the present study, we aimed to demonstrate whether LIPUS also ameliorates LV remodeling after acute myocardial infarction and if so, to elucidate the underlying molecular mechanisms involved in the beneficial effects of LIPUS. Approach and Results-We examined the effects of LIPUS on LV remodeling in a mouse model of acute myocardial infarction, where the heart was treated with either LIPUS or no-LIPUS 3 times in the first week (days 1, 3, and 5). The LIPUS improved mortality and ameliorated post-myocardial infarction LV remodeling in mice. The LIPUS upregulated the expression of vascular endothelial growth factor, endothelial nitric oxide synthase, phosphorylated ERK, and phosphorylated Akt in the infarcted area early after acute myocardial infarction, leading to enhanced angiogenesis. Microarray analysis in cultured human endothelial cells showed that a total of 1050 genes, including those of the vascular endothelial growth factor signaling and focal adhesion pathways, were significantly altered by the LIPUS. Knockdown with small interfering RNA of either β1-integrin or caveolin-1, both of which are known to play key roles in mechanotransduction, suppressed the LIPUS-induced upregulation of vascular endothelial growth factor. Finally, in caveolin-1-deficient mice, the beneficial effects of LIPUS on mortality and post-myocardial infarction LV remodeling were absent. Conclusions-These results indicate that the LIPUS therapy ameliorates post-myocardial infarction LV remodeling in mice in vivo, for which mechanotransduction and its downstream pathways may be involved. (Arterioscler Thromb Vasc

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“…36 Additionally, acoustic pressure levels employed in the present study fall into the range of acoustic pressure to which CAs are exposed in vivo. 37 F. Single-cell analysis of CA-free cell sonoporation Single-cell analysis was performed in order to investigate CA-free cell sonoporation using CMFDA, an intracellular low-molecular size (464.86 MW) membrane-impermeable fluorescent probe. The reduction of intracellular fluorescence intensity was quantified as an indicator of in situ CMFDA efflux induced by cell sonoporation.…”

Section: Temperature Monitoring During Applied Ultrasoundmentioning

confidence: 99%

Contrast agent-free sonoporation: The use of an ultrasonic standing wave microfluidic system for the delivery of pharmaceutical agents

et al. 2011

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Sonoporation is a useful biophysical mechanism for facilitating the transmembrane delivery of therapeutic agents from the extracellular to the intracellular milieu. Conventionally, sonoporation is carried out in the presence of ultrasound contrast agents, which are known to greatly enhance transient poration of biological cell membranes. However, in vivo contrast agents have been observed to induce capillary rupture and haemorrhage due to endothelial cell damage and to greatly increase the potential for cell lysis in vitro. Here, we demonstrate sonoporation of cardiac myoblasts in the absence of contrast agent (CA-free sonoporation) using a low-cost ultrasound-microfluidic device. Within this device an ultrasonic standing wave was generated, allowing control over the position of the cells and the strength of the acoustic radiation forces. Real-time single-cell analysis and retrospective postsonication analysis of insonated cardiac myoblasts showed that CA-free sonoporation induced transmembrane transfer of fluorescent probes (CMFDA and FITC-dextran) and that different mechanisms potentially contribute to membrane poration in the presence of an ultrasonic wave. Additionally, to the best of our knowledge, we have shown for the first time that sonoporation induces increased cell cytotoxicity as a consequence of CA-free ultrasound-facilitated uptake of pharmaceutical agents (doxorubicin, luteolin, and apigenin). The US-microfluidic device designed here provides an in vitro alternative to expensive and controversial in vivo models used for early stage drug discovery, and drug delivery programs and toxicity measurements.

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The role of Ca2+ in ultrasound-elicited bioeffects: progress, perspectives and prospects

Cited by 80 publications

References 100 publications

Understanding ultrasound induced sonoporation: Definitions and underlying mechanisms

Understanding ultrasound induced sonoporation: Definitions and underlying mechanisms

Low-Intensity Pulsed Ultrasound Enhances Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Mouse Model of Acute Myocardial Infarction

Contrast agent-free sonoporation: The use of an ultrasonic standing wave microfluidic system for the delivery of pharmaceutical agents

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