Nox4 as a novel therapeutic target for diabetic vascular complications

Diabetic vascular complications can affect both microvascular and macrovascular. Diabetic microvascular complications, such as diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, and diabetic cardiomyopathy, are believed to be caused by oxidative stress. The Nox family of NADPH oxidases is a significant source of reactive oxygen species and plays a crucial role in regulating redox signaling, particularly in response to high glucose and diabetes mellitus. This review aims to provide an overview of the current knowledge about the role of Nox4 and its regulatory mechanisms in diabetic microangiopathies. Especially, the latest novel advances in the upregulation of Nox4 that aggravate various cell types within diabetic kidney disease will be highlighted. Interestingly, this review also presents the mechanisms by which Nox4 regulates diabetic microangiopathy from novel perspectives such as epigenetics. Besides, we emphasize Nox4 as a therapeutic target for treating microvascular complications of diabetes and summarize drugs, inhibitors, and dietary components targeting Nox4 as important therapeutic measures in preventing and treating diabetic microangiopathy. Additionally, this review also sums up the evidence related to Nox4 and diabetic macroangiopathy.

Automated summary

This review provides an overview of the role and regulatory mechanisms of Nox4 in diabetic microangiopathy, with a special emphasis on its upregulation in diabetic nephropathy. It also presents novel perspectives, such as epigenetics, on how Nox4 regulates diabetic microangiopathy. Additionally, the review discusses Nox4 as a therapeutic target and highlights drugs, inhibitors, and dietary components that target Nox4 for the prevention and treatment of diabetic microangiopathy.