Lottonen-Raikaslehto Line, Rissanen Riina, Gurzeler Erika, Merentie Mari, Huusko Jenni, Schneider Jurgen E, Liimatainen Timo, Ylä-Herttuala Seppo
Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Radcliffe Department of Medicine, Division of Cardiovascular Medicine, University of Oxford, United kingdom.
Physiol Rep. 2017 Mar;5(6). doi: 10.14814/phy2.13096.
Cardiac-specific overexpression of vascular endothelial growth factor (VEGF)-B is 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-B and 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 (T ) in cardiovascular magnetic resonance imaging could be suitable for detecting severe fibrosis in the heart. We conclude that cardiac-specific overexpression of VEGF-B leads to left ventricular remodeling at early age and is a suitable model to study heart failure development with different imaging methods.
已知血管内皮生长因子(VEGF)-B在心脏特异性过表达会因脂质代谢改变而诱导左心室肥厚,其中神经酰胺在心脏中蓄积并导致线粒体损伤。本研究的目的是评估和比较不同的成像方法,以找到在早期诊断导致心力衰竭的进行性左心室重构的最敏感方法。在几个时间点,对5至14月龄的心脏特异性过表达VEGF-B的转基因小鼠和野生型小鼠的心脏进行超声心动图和心血管磁共振成像比较。通过分子生物学方法和组织学验证疾病进展。我们发现,转基因小鼠在5月龄时左心室重构就已开始,到14月龄时导致心力衰竭。超声心动图和心血管磁共振成像测量显示转基因小鼠心脏结构和功能有相似变化。组织学、基因表达和心电图的变化支持左心室肥厚的进展。心血管磁共振成像中的旋转框架纵向弛豫时间(T)可能适合检测心脏中的严重纤维化。我们得出结论,VEGF-B在心脏特异性过表达会在早期导致左心室重构,是使用不同成像方法研究心力衰竭发展的合适模型。