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

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http://hdl.handle.net/10138/199216

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Naumenko , N , Huusko , J , Tuomainen , T , Koivumaki , J T , Merentie , M , Gurzeler , E , Alitalo , K , Kivela , R , Yla-Herttuala , S & Tavi , P 2017 , ' Vascular Endothelial Growth Factor-B Induces a Distinct Electrophysiological Phenotype in Mouse Heart ' , Frontiers in Physiology , vol. 8 , 373 . https://doi.org/10.3389/fphys.2017.00373

Title: Vascular Endothelial Growth Factor-B Induces a Distinct Electrophysiological Phenotype in Mouse Heart
Author: Naumenko, Nikolay; Huusko, Jenni; Tuomainen, Tomi; Koivumaki, Jussi T.; Merentie, Mari; Gurzeler, Erika; Alitalo, Kari; Kivela, Riikka; Yla-Herttuala, Seppo; Tavi, Pasi
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
Date: 2017-05-31
Language: eng
Number of pages: 10
Belongs to series: Frontiers in Physiology
ISSN: 1664-042X
URI: http://hdl.handle.net/10138/199216
Abstract: Vascular endothelial growth factor B (VEGF-B) is a potentmediator 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 knownmodulatory 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.
Subject: cardiac myocytes
growth factors
EC-coupling
energy metabolism
ion channels
action potential
SODIUM-CHANNEL NA(V)1.5
CARDIAC-HYPERTROPHY
MICE
ARRHYTHMIAS
ISCHEMIA
DISEASE
MODEL
ARRHYTHMOGENESIS
REPOLARIZATION
OVEREXPRESSION
3111 Biomedicine
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