T-cell regulation of cardiac remodeling

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Veterans have 2-times higher risk of developing cardiovascular disease compared to non-veterans. For veterans who have a heart attacked (myocardial infarction; MI), 1 in 3 will not survive 1 year after the event compared to 1 in 10 in the general population. The goal of my project is to understand how the wound healing response after MI can promote the development of heart failure. My focus is the innate immune response, specifically the role of CD8+ T-cells. My central hypothesis is that CD8+ effector T- cells regulate PMN physiology through MMP-9 to induce adverse remodeling post-MI. Aim 1 will determine the role of CD8+ T-cells on the neutrophil physiology using cellular proteomics coupled with ex vivo experiments. Aim 2 will determine the role CD8+ T-cells in vivo focusing on how CD8+ T-cell effector subtypes and the secretion of MMP-9 effect long term cardiac function and survival post-MI. This is the first proposal to integrate multidisciplinary approaches to evaluate CD8+ T-cells in the MI setting. This study will add to our 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 VA Healthcare System by providing molecular knowledge to clinical practices so that the VA Healthcare System can continue to provide exceptional health care that improves Veteran health and well-being.