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dc.contributor.authorNaumenko N
dc.contributor.authorHuusko J
dc.contributor.authorTuomainen T
dc.contributor.authorKoivumäki JT
dc.contributor.authorMerentie M
dc.contributor.authorGurzeler E
dc.contributor.authorAlitalo K
dc.contributor.authorKivelä R
dc.contributor.authorYlä-Herttuala S
dc.contributor.authorTavi P
dc.date.accessioned2017-11-17T09:41:18Z
dc.date.available2017-11-17T09:41:18Z
dc.date.issued2017
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/4920
dc.description.abstractVascular endothelial growth factor B (VEGF-B) is a potent mediator of vascular, metabolic, growth, and stress responses in the heart, but the effects on cardiac muscle and cardiomyocyte function are not known. The purpose of this study was to assess the effects of VEGF-B on the energy metabolism, contractile, and electrophysiological properties of mouse cardiac muscle and cardiac muscle cells. In vivo and ex vivo analysis of cardiac-specific VEGF-B TG mice indicated that the contractile function of the TG hearts was normal. Neither the oxidative metabolism of isolated TG cardiomyocytes nor their energy substrate preference showed any difference to WT cardiomyocytes. Similarly, myocyte Ca2+ signaling showed only minor changes compared to WT myocytes. However, VEGF-B overexpression induced a distinct electrophysiological phenotype characterized by ECG changes such as an increase in QRSp time and decreases in S and R amplitudes. At the level of isolated TG cardiomyocytes, these changes were accompanied with decreased action potential upstroke velocity and increased duration (APD60–70). These changes were partly caused by downregulation of sodium current (INa) due to reduced expression of Nav1.5. Furthermore, TG myocytes had alterations in voltage-gated K+ currents, namely decreased density of transient outward current (Ito) and total K+ current (Ipeak). At the level of transcription, these were accompanied by downregulation of Kv channel-interacting protein 2 (Kcnip2), a known modulatory subunit for Kv4.2/3 channel. Cardiac VEGF-B overexpression induces a distinct electrophysiological phenotype including remodeling of cardiomyocyte ion currents, which in turn induce changes in action potential waveform and ECG.en
dc.language.isoENen
dc.publisherFrontiers Media SAen
dc.relation.ispartofseriesFrontiers in Physiologyen
dc.relation.urihttp://dx.doi.org/10.3389/fphys.2017.00373en
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/en
dc.titleVascular Endothelial Growth Factor-B Induces a Distinct Electrophysiological Phenotype in Mouse Hearten
dc.description.versionpublished versionen
dc.contributor.departmentA.I. Virtanen -instituutti / Bioteknologia ja molekulaarinen lääketiedeen
dc.contributor.departmentA.I. Virtanen -instituuttien
uef.solecris.id47977567en
dc.type.publicationinfo:eu-repo/semantics/articleen
dc.rights.accessrights© Authorsen
dc.relation.doi10.3389/fphys.2017.00373en
dc.description.reviewstatuspeerRevieweden
dc.relation.articlenumber373en
dc.relation.issn1664-042Xen
dc.relation.volume8en
dc.rights.accesslevelopenAccessen
dc.type.okmA1en
dc.type.versioninfo:eu-repo/semantics/publishedVersionen


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