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Exosomes induce and reverse monocrotaline-induced pulmonary hypertension in mice

Cardiovascular research, 2016-06, Vol.110 (3), p.319-330 [Peer Reviewed Journal]

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com. ;Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com. 2016 ;ISSN: 0008-6363 ;EISSN: 1755-3245 ;DOI: 10.1093/cvr/cvw054 ;PMID: 26980205

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Title:
Exosomes induce and reverse monocrotaline-induced pulmonary hypertension in mice
Author: Aliotta, Jason M ; Pereira, Mandy ; Wen, Sicheng ; Dooner, Mark S ; Del Tatto, Michael ; Papa, Elaine ; Goldberg, Laura R ; Baird, Grayson L ; Ventetuolo, Corey E ; Quesenberry, Peter J ; Klinger, James R
Subjects: Animals ; Case-Control Studies ; Cell-Derived Microparticles - metabolism ; Cell-Derived Microparticles - transplantation ; Cells, Cultured ; Disease Models, Animal ; Exosomes - genetics ; Exosomes - transplantation ; Familial Primary Pulmonary Hypertension - genetics ; Familial Primary Pulmonary Hypertension - physiopathology ; Gene Expression Regulation ; Humans ; Hypertension, Pulmonary - chemically induced ; Hypertension, Pulmonary - genetics ; Hypertension, Pulmonary - physiopathology ; Hypertension, Pulmonary - prevention & control ; Hypertrophy, Right Ventricular - chemically induced ; Hypertrophy, Right Ventricular - genetics ; Hypertrophy, Right Ventricular - prevention & control ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells - metabolism ; Mice, Inbred C57BL ; MicroRNAs - genetics ; Monocrotaline ; Original ; Pulmonary Artery - metabolism ; Pulmonary Artery - physiopathology ; Vascular Remodeling
Is Part Of: Cardiovascular research, 2016-06, Vol.110 (3), p.319-330
Description: Extracellular vesicles (EVs) from mice with monocrotaline (MCT)-induced pulmonary hypertension (PH) induce PH in healthy mice, and the exosomes (EXO) fraction of EVs from mesenchymal stem cells (MSCs) can blunt the development of hypoxic PH. We sought to determine whether the EXO fraction of EVs is responsible for modulating pulmonary vascular responses and whether differences in EXO-miR content explains the differential effects of EXOs from MSCs and mice with MCT-PH. Plasma, lung EVs from MCT-PH, and control mice were divided into EXO (exosome), microvesicle (MV) fractions and injected into healthy mice. EVs from MSCs were divided into EXO, MV fractions and injected into MCT-treated mice. PH was assessed by right ventricle-to-left ventricle + septum (RV/LV + S) ratio and pulmonary arterial wall thickness-to-diameter (WT/D) ratio. miR microarray analyses were also performed on all EXO populations. EXOs but not MVs from MCT-injured mice increased RV/LV + S, WT/D ratios in healthy mice. MSC-EXOs prevented any increase in RV/LV + S, WT/D ratios when given at the time of MCT injection and reversed the increase in these ratios when given after MCT administration. EXOs from MCT-injured mice and patients with idiopathic pulmonary arterial hypertension (IPAH) contained increased levels of miRs-19b,-20a,-20b, and -145, whereas miRs isolated from MSC-EXOs had increased levels of anti-inflammatory, anti-proliferative miRs including miRs-34a,-122,-124, and -127. These findings suggest that circulating or MSC-EXOs may modulate pulmonary hypertensive effects based on their miR cargo. The ability of MSC-EXOs to reverse MCT-PH offers a promising potential target for new PAH therapies.
Publisher: England: Oxford University Press
Language: English
Identifier: ISSN: 0008-6363
EISSN: 1755-3245
DOI: 10.1093/cvr/cvw054
PMID: 26980205
Source: GFMER Free Medical Journals
MEDLINE
Alma/SFX Local Collection

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Exosomes induce and reverse monocrotaline-induced pulmonary hypertension in mice

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