224 THE MAMMALIAN STE20-LIKE KINASE 2 (MST2), A CENTRAL MODULATOR OF THE HIPPO PATHWAY, MODULATES STRESS-INDUCED CARDIAC HYPERTROPHY

Because of its key role in the development of heart failure, cardiac hypertrophy becomes one of the main focuses of current research. The Hippo signalling pathway has recently moved to centre stage in this field because of it plays major role in cardiomyocyte proliferation and regeneration of the embryonic and newborn heart. However, its role in remodelling of the adult heart is less clear. Here we use an integrative biology approach incorporating molecular, cellular, in vivo animal model and translational bench to bedside research to characterise the role of mammalian STE20-like kinase 2 (Mst2), one of the two mammalian orthologs of Drosophila hippo, in cardiac hypertrophy. Mice with genetic ablation of Mst2 gene (Mst2−/−) exhibited a significant reduction of hypertrophy in response to transverse aortic constriction (TAC): heart weight/tibia length ratio after 2 weeks TAC: Mst2−/−, 7.32 mg/mm vs wild type (WT), 8.35 mg/mm, n=8, P