Email updates

Keep up to date with the latest news and content from Vascular Cell and BioMed Central.

Open Access Research

The angiogenic response is dependent on ultrasound contrast agent concentration

Chenara A Johnson1 and William D O’Brien123*

Author Affiliations

1 Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA

2 Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA

3 Bioacoustics Research Laboratory, Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, 405 N. Mathews, Urbana, IL 61801, 217/333-2407, USA

For all author emails, please log on.

Vascular Cell 2012, 4:10  doi:10.1186/2045-824X-4-10

Published: 15 May 2012

Abstract

Objective

Ultrasound (US) and ultrasound contrast agents (UCAs) provide a way to noninvasively induce targeted angiogenesis. However, there exists a lack of understanding regarding the mechanisms of this process that has impeded progress. This study sought to characterize the angiogenic response, by both exploring the role of UCA concentration ([UCA]) in bioeffect induction at 0 days post exposure (DPE) and assessing the bioeffect as a possible potentiator of angiogenesis at 5 DPE.

Methods

A 1-MHz ultrasonic transducer was used to expose the gracilis muscles of Sprague Dawley rats for 5 min with a 10-μs pulse duration, 10-Hz pulse repetition frequency, and 0.7-MPa peak rarefactional acoustic pressure (pr). Four [UCA]s were tested: 0x (saline), 1×, 5×, and 10×, where 1× is 5% Definity by volume of solution. Evans blue dye (EBD) was used to quantify changes in acute vascular permeability (0 DPE), and VEGF expression was quantified at 5 DPE to support that angiogenesis had occurred. CD31 staining was used to assess capillary density at both time points.

Results

[UCA] was a significant parameter for determining EBD leakage (permeability) and VEGF expression (p < 0.001 for both). However, [UCA] was not a significant parameter for capillary density at 0 or 5 DPE. Multiple comparisons between 0 and 5 DPE showed that only 10× [UCA] at 5 DPE was significantly different than 0 DPE, suggesting a [UCA] dependence of the angiogenic response.

Conclusions

This study suggests that [UCA] was a significant parameter in the induction of an angiogenic response with US and UCAs. It also suggests that rather than damage from US and UCAs, as previously speculated, a nondestructive mechanical interaction between the UCAs and vascular endothelium induces bioeffects to potentiate the angiogenic response.

Keywords:
Angiogenesis; VEGF; Ultrasound-induced bioeffects; Ultrasound contrast agent; Proangiogenic therapy; Therapeutic ultrasound