Abstract 19468: Overexpression of O-GlcNAcase in Coronary Endothelial Cells Improves Cardiac Contractility in Type 2 Diabetes

Ischemic heart disease is the leading cause of death in diabetic patients and coronary endothelial dysfunction plays a crucial role in the development and progression of ischemic heart disease. Excessive protein O-GlcNAcylation is observed in diabetic patients and it contributes to the functional changes in many tissues. To define the role of protein O-GlcNAcylation in coronary endothelial functions in diabetes, we used our unique transgenic mouse, endothelial cell (EC)-specific tet-inducible O-GlcNAcase (OGA, an enzyme which decreases protein O-GlcNAcylation) mouse and crossed it with TALLYHO mouse (TH mouse, a polygenic model for type 2 diabetes). TH mice exhibited increased apoptotic ECs and reduced capillary density in the left ventricular (LV) compared to the wild-type (WT) mice. Myocardial infarct size after ischemia/reperfusion was increased and cardiac functions were attenuated in TH mice compared to WT mice. Mouse coronary ECs (MCECs) isolated from TH mice showed higher protein O-GlcNAcylation th...