Gollmann-Tepeköylü, C;
Pölzl, L;
Graber, M;
Hirsch, J;
Nägele, F;
Lobenwein, D;
Hess, MW;
... Holfeld, J; + view all
(2020)
miR-19a-3p containing exosomes improve function of ischemic myocardium upon shock wave therapy.
Cardiovascular Research
, 116
(6)
pp. 1226-1236.
10.1093/cvr/cvz209.
Preview |
Text
Davidson_Shockwave for IRIS.pdf - Accepted Version Download (941kB) | Preview |
Abstract
AIMS: As many current approaches for heart regeneration exert unfavorable side-effects, the induction of endogenous repair mechanisms in ischemic heart disease is of particular interest. Recently, exosomes carrying angiogenic miRNAs have been described to improve heart function. However, it remains challenging to stimulate specific release of reparative exosomes in ischemic myocardium. In the present study, we sought to test the hypothesis that the physical stimulus of shock wave therapy (SWT) causes the release of exosomes. We aimed to substantiate the pro-angiogenic impact of the released factors, to identify the nature of their cargo, and to test their efficacy in vivo supporting regeneration and recovery after myocardial ischemia. METHODS AND RESULTS: Mechanical stimulation of ischemic muscle via SWT caused extracellular vesicle (EV) release from endothelial cells both in vitro and in vivo. Characterization of EVs via electron microscopy, nanoparticle tracking analysis and flow cytometry revealed specific exosome morphology and size with presence of exosome markers CD 9, CD81 and CD63. Exosomes exhibited angiogenic properties activating protein kinase b (Akt) and extracellular-signal regulated kinase (ERK) resulting in enhanced endothelial tube formation and proliferation. A miRNA array and transcriptome analysis via next-generation sequencing were performed to specify exosome content. miR-19a-3p was identified as responsible cargo, antimir-19a-3p antagonized angiogenic exosome effects. Exosomes and target miRNA were injected intramyocardially in mice after left anterior descending artery (LAD) ligation. Exosomes resulted in improved vascularization, decreased myocardial fibrosis and increased left ventricular ejection fraction as shown by transthoracic echocardiography. CONCLUSIONS: The mechanical stimulus of SWT causes release of angiogenic exosomes. miR-19a-3p is the vesicular cargo responsible for the observed effects. Released exosomes induce angiogenesis, decrease myocardial fibrosis and improve left ventricular function after myocardial ischemia. Exosome release via SWT could develop an innovative approach for the regeneration of ischemic myocardium.
| Type: | Article |
|---|---|
| Title: | miR-19a-3p containing exosomes improve function of ischemic myocardium upon shock wave therapy |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/cvr/cvz209 |
| Publisher version: | https://doi.org/10.1093/cvr/cvz209 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | angiogenesis, ischemia, ventricular function, left, left ventricular ejection fraction, myocardial ischemia, anterior descending branch of left coronary artery, myocardial fibrosis, endothelial cells, flow cytometry, endothelium, gene expression profiling, ligation, phosphotransferases, heart, mice, echocardiography, transthoracic, cardiac function, proto-oncogene proteins c-akt, exosomes, cd63 antigen, adverse effects, extracorporeal shockwave therapy, micrornas, nanoparticles, massively-parallel genome sequencing, extracellular vesicles |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10080457 |
Archive Staff Only
 |
View Item |
