Grant: New Investigator Salary Award - PA: Regional Partnerships Program - Saskatchewan

The development and progression of heart disease has been associated with the generation of toxic oxygen compounds, known as reactive oxygen species (ROS). These ROS can be produced in every cell of the heart and cause a high degree of damage to the cells and even death. The process by which damage to the cells and the heart occurs remains unknown. ROS can act on proteins responsible for contractility (contractile proteins) of the heart and modify them. I hypothesize that these contractile proteins will be more likely to be broken down by other proteins (proteolytic enzymes) and this break down of contractile proteins is responsible for the abnormal contraction (contractile dysfunction) of the heart after a heart attack (myocardial infarction). The major objectives are: (1) Determine if the use of drugs that prevent modification of proteins by toxic oxygen compounds (ROS) or inhibit the proteins responsible for protein break down (proteolytic enzymes) can protect the heart against cardiac contractile dysfunction (abnormal heart contractility. (2) Determine if using a combination of these drugs in sub-protective doses will show an additive effect. The research proposed in this application will provide new and very important information that will help us understand the processes responsible for abnormal heart contraction observed in several heart diseases. Also, combining drugs that prevent generation of ROS, modification of proteins and activation of proteolytic enzymes will be a very important strategy for treating heart disease.