Nox4 as a novel therapeutic target for diabetic vascular complications
- PMID: 37321060
- PMCID: PMC10363438
- DOI: 10.1016/j.redox.2023.102781
Nox4 as a novel therapeutic target for diabetic vascular complications
Abstract
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.
Keywords: Diabetic vascular complications; Dietary strategies; Epigenetic regulation; Nox4; Nox4 inhibitors.
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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References
-
- Thum T., Fraccarollo D., Schultheiss M., et al. Endothelial nitric oxide synthase uncoupling impairs endothelial progenitor cell mobilization and function in diabetes. Diabetes. 2007;56(3):666–674. - PubMed
-
- Shen G.X. Oxidative stress and diabetic cardiovascular disorders: roles of mitochondria and NADPH oxidase. Can. J. Physiol. Pharmacol. 2010;88(3):241–248. - PubMed
-
- Gorin Y., Block K., Hernandez J., et al. Nox4 NAD(P)H oxidase mediates hypertrophy and fibronectin expression in the diabetic kidney. J. Biol. Chem. 2005;280(47):39616–39626. - PubMed
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