Molecular mechanisms of endothelial dysfunction in the diabetic heart

Our observations show that long term hyperglycaemia by the formation of AGE, but also short term hyperglycaemic periods ("glucose spikes") damage the endothelium of the heart in diabetes. The endothelium is exposed to oxidative stress. The simultaneous generation of NO and superoxide anions enables the reaction of both species to form peroxynitrite which has been identified as an important mediator for the transformation of endothelium from an anticoagulant to a procoagulant state. Together with a functional loss of endothelium these processes are assumed to impair the coronary perfusion and to provoke adaptive processes which finally lead to cardiac dysfunction and remodelling of cardiac structure (Figure 6) as it has been described for the heart in diabetes.