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dc.contributor.authorGao, Hui
dc.contributor.authorSong, Yang
dc.contributor.authorMachado, Roberto F.
dc.creatorGao, H.
dc.date.accessioned2019-07-19T20:45:05Z
dc.date.available2019-07-19T20:45:05Z
dc.date.issued2019-07-09
dc.identifier.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85068752486&origin=inward
dc.identifier.urihttp://hdl.handle.net/10713/10107
dc.description.abstractNicotinamide phosphoribosyltransferase (NAMPT) upregulation in human pulmonary artery endothelial cells (hPAECs) is associated with pulmonary arterial hypertension (PAH) progression and pulmonary vascular remodeling. The underlying mechanisms regulating NAMPT expression are still not clear. In this study, we aimed to study the regulation of NAMPT expression by microRNA410 (miR410) in hPAECs and explore the role of miR410 in the pathogenesis of experimental pulmonary hypertension. We show that miR410 targets the 3′ UTR of NAMPT and that, concomitant with NAMPT upregulation, miR410 is downregulated in lungs of mice exposed to hypoxia-induced pulmonary hypertension (HPH). Our results also demonstrate that miR410 directly inhibits NAMPT expression. Overexpression of miR410 in hPAECs inhibits basal and VEGF-induced proliferation, migration and promotes apoptosis of hPAECs, while miR410 inhibition via antagomirs has the opposite effect. Finally, administration of miR410 mimics in vivo attenuated induction of NAMPT in PAECs and prevented the development of HPH in mice. Our results highlight the role of miR410 in the regulation of NAMPT expression in hPAECs and show that miR410 plays a potential role in PAH pathobiology by targeting a modulator of pulmonary vascular remodeling. © 2019, The Author(s).en_US
dc.description.sponsorshipThis study was funded by the National Heart, Lung, and Blood Institute (NHLBI) grant number R01HL111656, R01HL127342 and R01HL133951en_US
dc.description.urihttps://www.doi.org/10.1038/s41598-019-46352-zen_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofScientific Reportsen_US
dc.subjectmicroRNA410en_US
dc.subjectpulmonary artery endothelial cellsen_US
dc.subject.meshVascular Remodelingen_US
dc.subject.meshNicotinamide Phosphoribosyltransferaseen_US
dc.titleMicroRNA410 Inhibits Pulmonary Vascular Remodeling via Regulation of Nicotinamide Phosphoribosyltransferaseen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41598-019-46352-z
dc.relation.volume9


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