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Deficiency of miR-409-3p improves myocardial neovascularization and function through modulation of DNAJB9/p38 MAPK signaling

dc.contributor.authorBestepe, Furkan
dc.contributor.authorFritsche, Colette
dc.contributor.authorLakhotiya, Kartik
dc.contributor.authorNiosi, Carolyn E.
dc.contributor.authorGhanem, George F.
dc.contributor.authorMartin, Gregory L.
dc.contributor.authorPal-Ghosh, Ruma
dc.contributor.authorBecker-Greene, Dakota
dc.contributor.authorWeston, James
dc.contributor.authorHollan, Ivana
dc.contributor.authorRisnes, Ivar
dc.contributor.authorRynning, Stein Erik
dc.contributor.authorSolheim, Liv Heidi
dc.contributor.authorFeinberg, Mark W.
dc.contributor.authorBlanton, Robert M.
dc.contributor.authorIcli, Basak
dc.date.accessioned2023-11-08T08:22:42Z
dc.date.available2023-11-08T08:22:42Z
dc.date.created2023-06-16T12:17:46Z
dc.date.issued2023
dc.identifier.citationMolecular Therapy - Nucleic Acids. 2023, 32 995-1009.en_US
dc.identifier.issn2162-2531
dc.identifier.urihttps://hdl.handle.net/11250/3101261
dc.description.sponsorshipAngiogenesis is critical for tissue repair following myocardial infarction (MI), which is exacerbated under insulin resistance or diabetes. MicroRNAs are regulators of angiogenesis. We examined the metabolic regulation of miR-409-3p in post-infarct angiogenesis. miR-409-3p was increased in patients with acute coronary syndrome (ACS) and in a mouse model of acute MI. In endothelial cells (ECs), miR-409-3p was induced by palmitate, while vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) decreased its expression. Overexpression of miR-409-3p decreased EC proliferation and migration in the presence of palmitate, whereas inhibition had the opposite effects. RNA sequencing (RNA-seq) profiling in ECs identified DNAJ homolog subfamily B member 9 (DNAJB9) as a target of miR-409-3p. Overexpression of miR-409-3p decreased DNAJB9 mRNA and protein expression by 47% and 31% respectively, while enriching DNAJB9 mRNA by 1.9-fold after Argonaute2 microribonucleoprotein immunoprecipitation. These effects were mediated through p38 mitogen-activated protein kinase (MAPK). Ischemia-reperfusion (I/R) injury in EC-specific miR-409-3p knockout (KO) mice (miR-409ECKO) fed a high-fat, high-sucrose diet increased isolectin B4 (53.3%), CD31 (56%), and DNAJB9 (41.5%). The left ventricular ejection fraction (EF) was improved by 28%, and the infarct area was decreased by 33.8% in miR-409ECKO compared with control mice. These findings support an important role of miR-409-3p in the angiogenic EC response to myocardial ischemia.en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/deed.no*
dc.titleDeficiency of miR-409-3p improves myocardial neovascularization and function through modulation of DNAJB9/p38 MAPK signalingen_US
dc.title.alternativeDeficiency of miR-409-3p improves myocardial neovascularization and function through modulation of DNAJB9/p38 MAPK signalingen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.description.versionpublishedVersionen_US
dc.source.pagenumber995-1009en_US
dc.source.volume32en_US
dc.source.journalMolecular Therapy - Nucleic Acidsen_US
dc.identifier.doi10.1016/j.omtn.2023.05.021
dc.identifier.cristin2155248
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1


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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
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