NFAT5 and Hyperglycemia: These findings suggest that (a) diabetes and hypercholesterolaemia add on and perhaps synergize in inducing aortic stiffening; (b) the biomechanical stretch due to hyperglycaemia‐induced hyperosmolar stress is specifically associated with aortic stiffening in diabetes; and (c) the hypertonicity‐responsive transcription factor NFAT5 may play a key role in cytoskeletal remodelling and the subsequent arterial stiffening in diabetes.