Cardiac development and remodelling in Magic-F1 transgenic mice

Abstract

MAGIC-F1 (Met Activating Genetically Improved Chimeric Factor 1) is a human recombi- nant protein, derived from dimerization of the receptor-binding domain of hepatocyte growth factor (HGF). Previous experiments demonstrated that skeletal muscle specific expression of Magic-F1 can induce constitutive muscular hypertrophy, improve running performance and accelerate muscle regeneration after injury in hemizigous transgenic mice [1]. Furthermore, the microarray analysis of Magic-F1+/+ satellite cells showed transcriptomic changes in genes involved in the control of muscle growth, development and vascularisation [2].

In this study we demonstrate that Magic-F1 mice show an alteration of the heart morphol- ogy. Morphometric analysis and three-dimensional reconstruction of the hearth revealed that MAGIC-F1 paracrine effect is able to induce a robust remodelling of the left ventricle cham- ber in transgenic mice. Interestingly, we found in Magic-F1 hearts an alteration of Phd2 and HIF1 protein levels. These two oxygen sensors are found dysregulated in cardiac ischaemic conditions, where generalised hypoxia causes functional impairments in cardiomyocytes and structural tissue damage [3-4]. These preliminary results support the involvement of oxygen sensors in Magic-F1-induced cardiac hypertrophy and dilation. In addition, Magic-F1+/+ mice can be used as non-pressure overload model to further investigate the role of oxygen-sensors in ischaemic heart disease. To better understand the biological effects of MAGIC-F1 on the mor- phology and function of cardiac muscle, more detailed studies are required. It could be also interesting to have a longer follow-up of the homozygous animals, to investigate the progres- sion of the cardiac remodelling upon a double dose of MAGIC-F1.