Thorp Project Summary Abstract Cardiac injury and heart failure are significant causes of morbidity and mortality. Enhanced therapeutic strategies that are informed by new discoveries in the fundamental mechanisms of biology have the potential to enhance tissue repair and improve health. Diverse risk factors including age, sex, diet, and hypertension can affect disease outcome. Within this framework, common underlying factors of disease progression are inflammation and cells of the innate immune system. This includes myeloid phagocytes, which have the capacity to be either cardioprotective or cardiopathogenic. After myocardial injury, the extent of inflammation and the activation state of myeloid macrophages have been linked to the degree of myocardial stress, cardiac fibrosis, and cardiac performance. One explanation for this is the ability of macrophage subsets to secrete potent cytokines which regulate the activity of nearby cells, such as parechymal, stromal, and neighboring immune cells of the heart. Our studies will identify novel roles for macrophage subsets and intercellular crosstalk by signaling through vascular endothelial growth factors, as well as integrated contributions of mitochondrial immunometabolism.