A Possible Target of Antioxidative Therapy for Diabetic Vascular Complications-Vascular NAD(P)H Oxidase

• Published in: Current medicinal chemistry Vol. 10; no. 17; pp. 1759 - 1764
• Main Authors: INOGUCHI, T, TSUBOUCHI, H, SATO, N, SEKIGUCHI, N, KOBAYASHI, K, NAWATA, H, ETOH, T, KAKIMOTO, M, SONTA, T, UTSUMI, H, SUMIMOTOI, H, YU, H. Y, SONODA, N, INUO, M
• Format: Journal Article
• Language: English
• Published: Schiphol Bentham Science Publishers Ltd 01.09.2003; Bentham Science
• Subjects: Animals; Antioxidants - metabolism; Antioxidants - therapeutic use; Associated diseases and complications; Biological and medical sciences; Diabetes. Impaired glucose tolerance; Diabetic Angiopathies - drug therapy; Diabetic Angiopathies - enzymology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelium, Vascular - drug effects; Endothelium, Vascular - enzymology; Enzyme Activation - drug effects; Enzyme Inhibitors - therapeutic use; Glucose - pharmacology; Humans; Medical sciences; NADPH Oxidases - antagonists & inhibitors; NADPH Oxidases - metabolism; Oxidative stress; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - pharmacology; Reactive Oxygen Species - metabolism; Endocrinopathy; NADPH; Oxidative stress; Protein kinase C; Pathophysiology; Enzyme; Transferases; Diabetes mellitus; Oxidase; Cardiovascular disease; Statin derivative; Review; Antioxidant; Prevention; Vascular disease; Peptidases; Mitochondria; Peptidyl-dipeptidase A; DNA; Hydrolases; Peptidyl-dipeptidases; Complication; Oxidoreductases; Angiotensin II
• ISSN: 0929-8673; 1875-533X
• DOI: 10.2174/0929867033457133

A growing body of evidence has shown that oxidative stress may be involved in the development of vascular complications associated with diabetes. However, the molecular mechanism for increased reactive oxygen species (ROS) production in diabetes remains uncertain. Among various possible mechanisms, attention have increasingly been paid to NAD(P)H oxidase as the most important source of ROS production in vascular cells. High glucose level stimulates ROS production through protein kinase C (PKC)-dependent activation of vascular NAD(P)H oxidase. Furthermore, the expression of NAD(P)H oxidase components is increased in micro- and macrovascular tissues of diabetic animals in association with various functional disorders and histochemical abnormalities. These results suggest that vascular NAD(P)H oxidase-driven ROS production may contribute to the onset or development of diabetic micro- or macrovascular complications. In this point of view, the possible new strategy of antioxidative therapy for diabetic vascular complications is discussed in this review.