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Vascular Endothelial Growth Factor-B Induces a Distinct Electrophysiological Phenotype in Mouse Heart

Vascular 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, co...

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Autores principales: Naumenko, Nikolay, Huusko, Jenni, Tuomainen, Tomi, Koivumäki, Jussi T., Merentie, Mari, Gurzeler, Erika, Alitalo, Kari, Kivelä, Riikka, Ylä-Herttuala, Seppo, Tavi, Pasi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450225/
https://www.ncbi.nlm.nih.gov/pubmed/28620319
http://dx.doi.org/10.3389/fphys.2017.00373
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author Naumenko, Nikolay
Huusko, Jenni
Tuomainen, Tomi
Koivumäki, Jussi T.
Merentie, Mari
Gurzeler, Erika
Alitalo, Kari
Kivelä, Riikka
Ylä-Herttuala, Seppo
Tavi, Pasi
author_facet Naumenko, Nikolay
Huusko, Jenni
Tuomainen, Tomi
Koivumäki, Jussi T.
Merentie, Mari
Gurzeler, Erika
Alitalo, Kari
Kivelä, Riikka
Ylä-Herttuala, Seppo
Tavi, Pasi
author_sort Naumenko, Nikolay
collection PubMed
description Vascular 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 Ca(2+) 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 (APD(60–70)). These changes were partly caused by downregulation of sodium current (I(Na)) due to reduced expression of Na(v)1.5. Furthermore, TG myocytes had alterations in voltage-gated K(+) currents, namely decreased density of transient outward current (I(to)) and total K(+) current (I(peak)). At the level of transcription, these were accompanied by downregulation of K(v) channel-interacting protein 2 (Kcnip2), a known modulatory subunit for K(v)4.2/3 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.
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spelling pubmed-54502252017-06-15 Vascular Endothelial Growth Factor-B Induces a Distinct Electrophysiological Phenotype in Mouse Heart Naumenko, Nikolay Huusko, Jenni Tuomainen, Tomi Koivumäki, Jussi T. Merentie, Mari Gurzeler, Erika Alitalo, Kari Kivelä, Riikka Ylä-Herttuala, Seppo Tavi, Pasi Front Physiol Physiology Vascular 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 Ca(2+) 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 (APD(60–70)). These changes were partly caused by downregulation of sodium current (I(Na)) due to reduced expression of Na(v)1.5. Furthermore, TG myocytes had alterations in voltage-gated K(+) currents, namely decreased density of transient outward current (I(to)) and total K(+) current (I(peak)). At the level of transcription, these were accompanied by downregulation of K(v) channel-interacting protein 2 (Kcnip2), a known modulatory subunit for K(v)4.2/3 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. Frontiers Media S.A. 2017-05-31 /pmc/articles/PMC5450225/ /pubmed/28620319 http://dx.doi.org/10.3389/fphys.2017.00373 Text en Copyright © 2017 Naumenko, Huusko, Tuomainen, Koivumäki, Merentie, Gurzeler, Alitalo, Kivelä, Ylä-Herttuala and Tavi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Naumenko, Nikolay
Huusko, Jenni
Tuomainen, Tomi
Koivumäki, Jussi T.
Merentie, Mari
Gurzeler, Erika
Alitalo, Kari
Kivelä, Riikka
Ylä-Herttuala, Seppo
Tavi, Pasi
Vascular Endothelial Growth Factor-B Induces a Distinct Electrophysiological Phenotype in Mouse Heart
title Vascular Endothelial Growth Factor-B Induces a Distinct Electrophysiological Phenotype in Mouse Heart
title_full Vascular Endothelial Growth Factor-B Induces a Distinct Electrophysiological Phenotype in Mouse Heart
title_fullStr Vascular Endothelial Growth Factor-B Induces a Distinct Electrophysiological Phenotype in Mouse Heart
title_full_unstemmed Vascular Endothelial Growth Factor-B Induces a Distinct Electrophysiological Phenotype in Mouse Heart
title_short Vascular Endothelial Growth Factor-B Induces a Distinct Electrophysiological Phenotype in Mouse Heart
title_sort vascular endothelial growth factor-b induces a distinct electrophysiological phenotype in mouse heart
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450225/
https://www.ncbi.nlm.nih.gov/pubmed/28620319
http://dx.doi.org/10.3389/fphys.2017.00373
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