Grant: Project Grant

Enlargement of the heart is one of the most common causes of heart failure in Canada. Once cardiac failure develops, the condition is irreversible and is associated with a very high death rate. Fifty percent of patients whose heart failure has progressed to include shortness of breath without physical activity do not survive beyond one year. As the heart becomes enlarged, it also disrupts the production of small lipid molecules that control the heart function, causing further damage and increasing the risk of sudden cardiac death. The heart enlargement reduces the production of the cardioprotective lipid molecules called epoxyeicosatrienoic acids and increases the production of cardiotoxic molecules called hydroxyeicosatetraenoic acid. While most patients can be treated with drug therapy, these treatments have side effects and are not effective in all patients. The objectives of our work are to control and prevent enlargement of the heart to improve treatment options for patients and reduce mortality. By increasing the production of the cardioprotective lipid molecules (epoxyeicosatrienoic acids) and inhibiting the production of cardiotoxic molecules (hydroxyeicosatetraenoic acid) in the heart, we can prevent the progressive deterioration of heart function and the development of heart failure. Our research will identify the molecules that are responsible for the enlargement of the heart and heart failure. In addition, we will test new chemicals that are known to increase the production of the cardioprotective lipid molecules and inhibit the production of cardiotoxic molecules in the heart. This will prevent the progressive deterioration of heart function and the development of heart failure. This research will help to diminish health care costs, as well as to design strategies that improve treatment of heart failure.