title: Left ventricular remodeling leads to heart failure in mice with cardiac-specific overexpression of VEGF-B167: echocardiography and magnetic resonance imaging study.
abstract: Cardiac-specific overexpression of vascular endothelial growth factor (VEGF)-B167is known to induce left ventricular hypertrophy due to altered lipid metabolism, in which ceramides accumulate to the heart and cause mitochondrial damage. The aim of this study was to evaluate and compare different imaging methods to find the most sensitive way to diagnose at early stage the progressive left ventricular remodeling leading to heart failure. Echocardiography and cardiovascular magnetic resonance imaging were compared for imaging the hearts of transgenic mice with cardiac-specific overexpression of VEGF-B167and wild-type mice from 5 to 14 months of age at several time points. Disease progression was verified by molecular biology methods and histology. We showed that left ventricular remodeling is already ongoing at the age of 5 months in transgenic mice leading to heart failure by the age of 14 months. Measurements from echocardiography and cardiovascular magnetic resonance imaging revealed similar changes in cardiac structure and function in the transgenic mice. Changes in histology, gene expressions, and electrocardiography supported the progression of left ventricular hypertrophy. Longitudinal relaxation time in rotating frame (T1ρ) in cardiovascular magnetic resonance imaging could be suitable for detecting severe fibrosis in the heart. We conclude that cardiac-specific overexpression of VEGF-B167leads to left ventricular remodeling at early age and is a suitable model to study heart failure development with different imaging methods.
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Line
authors.initials: L
authors.lastname: Lottonen-Raikaslehto
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Riina
authors.initials: R
authors.lastname: Rissanen
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Erika
authors.initials: E
authors.lastname: Gurzeler
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Merentie
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jenni
authors.initials: J
authors.lastname: Huusko
authors.affiliation: Radcliffe Department of Medicine, Division of Cardiovascular Medicine, University of Oxford, United kingdom.
authors.forename: Jurgen E
authors.initials: JE
authors.lastname: Schneider
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.|Clinical Imaging Center, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Liimatainen
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland seppo.ylaherttuala@uef.fi.|Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland.|Heart Center, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004452:Echocardiography; D004562:Electrocardiography; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D042561:Vascular Endothelial Growth Factor B / Q000235:genetics / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: C467485:VEGFB protein, human; D042561:Vascular Endothelial Growth Factor B
keywords: Cardiovascular imaging; heart failure; left ventricular hypertrophy; mouse ECG; vascular endothelial growth factor ‐B