Intravenous injection of extracellular vesicles to treat chronic myocardial ischemia
Open Access
- 11 September 2020
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 15 (9), e0238879
- https://doi.org/10.1371/journal.pone.0238879
Abstract
Mesenchymal stem cell-derived extracellular vesicles (EVs) appear to be a very exciting treatment option for heart disease. Here, we used a swine model of chronic myocardial ischemia to evaluate the efficacy of a less-invasive method of injection of EVs via a peripheral intravenous route. Sixteen Yorkshire swine underwent placement of an ameroid constrictor on the left circumflex (LCx) artery at age 11 weeks to induce chronic myocardial ischemia. Two weeks later, they were divided into two groups: control (CON; n = 8), and intravenous injection of EVs (EVIV; n = 8). At 18 weeks of age, animals underwent final analysis and euthanasia. The chronically ischemic myocardium (LCx territory) was harvested for analysis. Intravenous injection (IV) of EVs induced several pro-angiogenic markers such as MAPK, JNK but not Akt. Whereas IV injections of EVs decreased VEGFR2 expression and inhibited apoptotic signaling (caspase 3), they increased expression of VEGFR1 that is believed to be anti-angiogenic. Injection of EVs did not result in an increase in vessel density and blood flow when compared to the control group. Although IV injection of EVs upregulated several pro-angiogenic signaling pathways, it failed to induce changes in vascular density in the chronically ischemic myocardium. Thus, a lack of increase in vascular density at the doses tested failed to elicit a functional response in ischemic myocardium.Funding Information
- National Heart, Lung, and Blood Institute (R01HL46716)
- National Heart, Lung, and Blood Institute (RO1HL128831-01A1)
- American Heart Association (14GRNT20460291)
- National Heart, Lung, and Blood Institute (1R01HL133624-01A1)
- National Institute of General Medical Sciences (2T32 GM065085-12)
- National Institute of General Medical Sciences (2T32 GM065085-13)
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