Temporal effects of CD8 T-cells post-MI

Summary: For patients who have a heart attack (myocardial infarction; MI), 1 in 3 will not survive 5 years after the event. Therefore, there is a critical need to facilitate the long-term goal of providing potential intervention targets to prevent, slow, or reverse progression to heart failure in heart attack patients. The long-term goal of the proposal is to understand how CD8+ T-cells are impairing the wound healing response after MI leading to eventual development of heart failure. The specific objective is to understand the temporal changes in the genetic and physiological profiles of the CD8+ T-cell population and how this regulates cardiac wound healing after a heart attack. The central hypothesis is that temporal changes in CD8+ T-cell heterogeneity mediates alterations of the constitutive properties of the ischemic scar and subsequent ventricular dysfunction. Aim 1 will test the hypothesis that temporal regulation of CD8+ T-cell activation is a fundamental determinant of the constitutive properties of ischemia induced myocardial scar. Aim 2 will test the hypothesize that CD8+ T-cell downstream effects during post-MI remodeling are not fully regulated by antigen presentation. This proposal will take a cutting-edge and integrative multidisciplinary approach to evaluate CD8+ T-cells in the MI setting. The completion of the study will provide a better understanding of critical mechanisms underlying adverse effects of the adaptive immune response and wound healing after MI. The proposed study aligns with the mission of the healthcare system by providing molecular knowledge to clinical practices so that we can continue to provide exceptional health care that improves patient health and well-being.