There is increasing evidence that reactive oxygen species play a significant risk in diabetes associated compliactions, including micro-and macrovascular injury.

NADPH oxidases are the only enzymes which are dedicated to produce ROS.

We have identified that the NADPH oxidase Nox1 plays a pivotal role in development and progression of diabetes associated atherosclerosis. Interestingly Nox4 in the vasculature appears to play a protective role. In the kidney, Nox4 appears to de deleterious for albuminuria development and renal fibrosis. Genetic deficiency of Nox4 provided renoprotection and podocyte specific Nox4 deletion also attenuated albuminuria and renal fibrosis in diabetic nephropathy. Furthermore, novel Nox inhibitors such as GKT137831 have been developed and have shown atheroprotective and renoprotecive effects in intervention and prevention studies in diabetes. These drugs are currently in clinical phase IIb evaluation.

More recently, the human isoform Nox5 has been suggested to play a key role in diabetes associated complications.  We are currently exploring this isoform using unique Nox5 expressing mice in either endothelial or smooth muscle cells in the context of diabetes. It is expected that novel interventions targeting Nox derived ROS will  play a role in the future treatment of diabetes associated vascular complications.