Grant: Operating Grant

Despite the substantial progress that has been made during the past two decades in heart research, cardiac disease still represents a significant cause of morbidity and mortality in North America. When oxygen delivery to the heart muscle is decreased such as seen during heart attack or myocardial infarction, the cells of the heart begin to die by a genetically regulated process known as Apoptosis. This is a major clinical problem since once injured cardiac cells die they are not replaced by new ones. Consequently, the loss of heart cells through an apoptotic process decreases the heart's ability to pump blood which ultimately manifest as heart failure. Heart failure represents a major financial and socio-economic burden to Canada, since individuals with heart failure require costly long-term care. Understanding the signaling pathways and cellular factors that regulate cell death/survival processes in the heart would be of substantial importance toward developing new therapeutic agents that could prevent excess cardiac cell death and heart failure. The proposed studies will specifically address this issue by testing the postulated role of the cellular factor Nuclear factor -kB (NF-kB) as a survival factor in the heart. This innovative research will provide new important information regarding the molecular mechanisms that regulate cardiac cell survival during disease conditions. The long-term therapeutic objective of this research is directed toward improving the quality of life of patients with heart disease by developing novel agents that would reduce apoptosis during heart attack. The spin-off benefit to this research would be realized by a substantial reduction in costly medications and need for long-term patient care. It can be seen that this research will have a major and positive impact on society and Canada's health care system in particular.