Also, activation of ROS-generating NADPH oxidase isoforms in the heart by various stimuli during hyperglycemia including angiotensin II (Ang II), endothelin-1 (ET-1), cytokines and growth factors, appears to be important in redox-sensitive signalling leading to the accumulation of extracellular matrix (ECM) proteins, interstitial and perivascular fibrosis and myocyte hypertrophy causing LV remodelling [12], [13], [14], [15]. This evidence concerns the gene EDN1 and Hyperglycemia.