Investigation into the role of inositol 1,4,5-triphosphate mediated calcium release in controlling cardiac hypertrophy

Heart disease is a significant cause of mortality in the developed world. In 2004 it was responsible for 137,700 deaths in the UK, equating to 24 percent of all deaths. A major predictor of mortality due to heart disease is cardiac hypertrophy (an increase in cell size without increase in cell number), and it is the most important risk factor for heart failure in humans. Hypertrophy can however also be a beneficial adaptive response providing the increased blood supply required during pregnancy and to sustain levels of increased physical activity experienced by athletes. Cardiac hypertrophy is characterised by an increase in the muscle mass/size of the heart due to enlargement of heart cells without any proliferation. Calcium increases in the muscle cells of the heart control contraction and the activity of genes that determine heart size. Since during disease the heart can grow too much, causing it not to work so well and fail, it is important to understand how calcium can precisely regulate the genes' activity and heart contraction. Using microsocopy and molecular biology techniques, we will measure changes in cell calcium and gene activity associated with heart growth. The effect of modifying calcium changes upon heart growth will also be monitored. Using these approaches, we aim to understand how calcium can precisely control myocyte (muscle cell) transcription (the copying of DNA information into RNA) independent of its effects on contraction. Ultimately, drugs will be developed to control heart growth without affecting heart function.