Functional Activity and Endothelial-Lining Integrity of Ex Vivo Arteries Exposed to Ultrasound-Mediated Microbubble Destruction

J. Angel Navarro-Becerra*, Gabriel A. Caballero-Robledo, Carlos A. Franco-Urquijo, Amelia Ríos, Bruno Escalante

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2335-2348
Number of pages14
JournalUltrasound in Medicine and Biology
Volume46
Issue number9
DOIs
Publication statusPublished - Sept 2020

Bibliographical note

Funding Information:
This work was supported the Mexican Council for Science and Technology (CONACyT, grant number 1180 to B.E.). J.A.N.-B. and C.A.F.-U. are fellows with CONACyT.

Funding Information:
This work was supported the Mexican Council for Science and Technology (CONACyT, grant number 1180 to B.E.). J.A.N.-B. and C.A.F.-U. are fellows with CONACyT. The authors declare that there is no conflict of interest regarding the publication of this article.

Publisher Copyright:
© 2020 World Federation for Ultrasound in Medicine & Biology

All Science Journal Classification (ASJC) codes

  • Radiological and Ultrasound Technology
  • Biophysics
  • Acoustics and Ultrasonics

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