Ultrasound-Mediated Stimulation of Microbubbles after Acute Myocardial Infarction and Reperfusion Ameliorates Left-Ventricular Remodelling in Mice via Improvement of Borderzone Vascularization
Doerner J, Struck R, Zimmer S, Peigney C, Duerr GD, Dewald O, Kim SC, Malan D, Bettinger T, Nickenig G, Ghanem A (2013)
Publication Type: Journal article
Publication year: 2013
Journal
Book Volume: 8
Article Number: e56841
Journal Issue: 2
DOI: 10.1371/journal.pone.0056841
Abstract
Aims: Post-infarction remodelling (PIR) determines left-ventricular (LV) function and prognosis after myocardial infarction. The aim of this study was to evaluate transthoracic ultrasound-mediated microbubble stimulation (UMS) as a novel gene- and cell-free therapeutic option after acute myocardial infarction and reperfusion (AMI/R) in mice. Methods and Results: For myocardial delivery of UMS, a novel therapeutic ultrasound-system (TIPS, Philips Medical) and commercially available microbubbles (BR1, Bracco Suisse SA) were utilized in a closed-chest mouse model. UMS was performed as myocardial post-conditioning (PC) on day four after 30 minutes of coronary occlusion and reperfusion. LV-morphology, as well as global and regional function were measured repeatedly with reconstructive 3-dimensional echocardiography applying an additional low-dose dobutamine protocol after two weeks. Scar size was quantified by means of histomorphometry. A total of 41 mice were investigated; 17 received PC with UMS. Mean ejection fraction (EF) prior UMS was similar in both groups 53%±10 (w/o UMS) and 53%±14 (UMS, p = 0.5), reflecting comparable myocardial mass at risk 17%±8 (w/o UMS), 16%±13 (UMS, p = 0.5). Two weeks after AMI/R, mice undergoing UMS demonstrated significantly better global LV-function (EF = 53%±7) as compared to the group without PC (EF = 39%±11, p<0.01). The fraction of akinetic myocardial mass was significantly lower among mice undergoing UMS after AMI/R [27%±10 (w/o UMS), 13%±8 (UMS), p<0.001)]. Our experiments showed a fast onset of transient, UMS-induced upregulation of vascular-endothelial and insulin-like growth factor (VEGF-a, IGF-1), as well as caveolin-3 (Cav-3). The mice undergoing PC with UMS after AMI/R showed a significantly lower scar size. In addition, the microvascular density was significantly higher in the borderzone of UMS-treated animals. Conclusion: UMS following AMI/R ameliorates PIR in mice via up-regulation of VEGF-a, IGF-1 and Cav-3, and consecutive improvement of myocardial borderzone vascularization. © 2013 Dörner et al.
Authors with CRIS profile
Involved external institutions
Universitätsklinikum Bonn
Germany (DE)
Rheinische Friedrich-Wilhelms-Universität Bonn
Germany (DE)
Bracco Suisse SA
Switzerland (CH)
Germany (DE)
Rheinische Friedrich-Wilhelms-Universität Bonn
Germany (DE)
Bracco Suisse SA
Switzerland (CH)
How to cite
APA:
Doerner, J., Struck, R., Zimmer, S., Peigney, C., Duerr, G.D., Dewald, O.,... Ghanem, A. (2013). Ultrasound-Mediated Stimulation of Microbubbles after Acute Myocardial Infarction and Reperfusion Ameliorates Left-Ventricular Remodelling in Mice via Improvement of Borderzone Vascularization. PLoS ONE, 8(2). https://doi.org/10.1371/journal.pone.0056841
MLA:
Doerner, Jonas, et al. "Ultrasound-Mediated Stimulation of Microbubbles after Acute Myocardial Infarction and Reperfusion Ameliorates Left-Ventricular Remodelling in Mice via Improvement of Borderzone Vascularization." PLoS ONE 8.2 (2013).
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