Heart failure (HF) is a complex clinical syndrome, in which the heart is incapable of pumping an adequate amount of blood to meet the body's basic metabolic needs. It is a major public health problem, with a prevalence of more than 23 million worldwide. The current conventional pharmacological therapies have shown some efficacy in symptom relief and improving survival of HF patients. However, the overall efficacy of these therapies is somewhat limited as HF still progresses even in responsive patients. New therapeutic development is needed, which requires a deep understanding the mechanisms underlying the progression of HF. Using animal models that can simulate the complex pathophysiological changes of heart failure in humans and the change of cardiac remodelling and functional deterioration can be quantified we can gain a better understanding of this disease. The aim of my work at the University of Manchester is to use mouse models of cardiovascular disease combined with genetic manipulation to investigate signalling pathways involved in cardiac remodelling and heart failure. This thesis includes some of my work. It consists of four chapters. Chapter 1 is a general introduction to heart failure, briefly reviewing cardiac anatomy, physiology, pathophysiology and molecular mechanisms of heart failure, and the development of mouse models for heart failure research. Chapter 2 includes three studies regarding the application of mouse models to study mammalian gene function in health and disease, particularly in cardiac hypertrophy and heart failure research. The first study focuses on the EuroPhenome project, which is a free and comprehensive resource for raw and annotated high-throughput phenotyping data from genetically modified mouse lines. The second study analyses the genome and baseline physiological phenotypes of C57BL/6NTac mice compared with the widely used inbreed strain, C57BL/6J. The third study examines the pathophysiological response to pressure overload induced by transverse aortic constriction in these two strains. Data from this study demonstrated that C57BL/6NTac and C57BL/6J mice developed different styles of cardiac hypertrophy and developed heart failure in different time scales. Chapter 3 includes 10 publications showing novel findings about the critical roles of the extracellular signal-regulated protein kinase 2 (ERK2) and upstream mediator the mammalian ste-20-like kinase (Mst2), the extracellular signal-regulated protein kinase 5 (ERK5), and the mitogen-activated protein (MAP) kinase kinase 4/7 (MKK4/MKK7) and the MKK7 upstream mediator Pak1 in cardiac remodelling and functional maintenance under stress stimulation. Finally, a brief summary of these findings is given in Chapter 4 and their clinical significance is discussed. This work greatly contributes to the biomedical research community and advances the knowledge about the transition from cardiac remodelling to failure.