This National Heart, Lung, and Blood Institute (NHLBI) R01 grant award for $691,614 supports research by Rhode Island Hospital, a division of Lifespan Corporation, to investigate how diabetes-induced modifications to the enzyme CaMKII impact the function of small-conductance calcium-activated potassium (SK) channels in coronary microvascular endothelial cells. The goal is to identify novel pathways and molecular targets for improving coronary microvascular function in diabetic patients with coronary heart disease. The research will employ mouse models, cell-based assays, and in-vivo assessments of myocardial blood flow to elucidate how post-translational modifications to CaMKII, including oxidation, O-GlcNAcylation, and phosphorylation, dysregulate SK channel activity and impair endothelial-dependent coronary microvascular relaxation. This 4-year project falls under the NHLBI's Cardiovascular Diseases Research program (CFDA 93.837) and aims to identify novel therapeutic strategies for improving coronary microvascular function in the diabetic population.