Reactive oxygen species-selective regulation of aortic inflammatory gene expression in Type 2 diabetes

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 292; no. 5; pp. H2073 - H2082
• Main Authors: Martin, Alejandra San, Du, Pingfeng, Dikalova, Anna, Lassegue, Bernard, Aleman, Maria, Gongora, Maria Carolina, Brown, Kathryn, Joseph, Giji, Harrison, David G, Taylor, W. Robert, Jo, Hanjoong, Griendling, Kathy K
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.05.2007
• Subjects: Animals; Aorta - immunology; Aortitis - immunology; Cardiology; Cardiovascular disease; Cytokines; Diabetes; Diabetes Mellitus, Type 2 - immunology; Gene Expression; Gene Expression Regulation - immunology; Heart; Immunologic Factors - immunology; Mice; Mice, Inbred Strains; Reactive Oxygen Species - immunology; Rodents
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00943.2006

Division of Cardiology, Department of Medicine, Emory University, Atlanta, Georgia Submitted 31 August 2006 ; accepted in final form 16 January 2007 Vascular diseases are a major complication of diabetes mellitus (DM), although their etiology is poorly understood. NADPH oxidase-derived reactive oxygen species (ROS) production and inflammation are potential mediators of DM-associated vascular diseases. Using db/db mice as a Type 2 diabetes model, we examined the relationship between NADPH oxidase-derived ROS and vascular inflammation. When compared with control m +/+ mice, aortas from 4- and 12-wk-old db/db mice had higher NADPH oxidase activity and increased superoxide levels, leading to NADPH oxidase-dependent impaired vasodilation at 12 wk. Diabetes progression from 4 to 12 wk led to increased Nox1, Nox4, and p22 phox subunit mRNAs and induced the expression of a group of matrix remodeling-related cytokines: connective tissue growth factor (CTGF), bone morphogenetic protein 4 (BMP-4), and osteopontin (OPN). After 8 wk of treatment with the superoxide scavenger Tempol, 12-wk-old db/db mice had lower superoxide production, reduced plasma glucose and lipids, and lower BMP-4 and OPN protein expression when compared with nontreated mice. No changes were observed with Tempol in CTGF or m +/+ mice. The ability of Tempol to reverse ROS production as well as OPN and BMP-4, but not CTGF, induction suggests that DM-induced vascular inflammation involves both ROS-sensitive and -insensitive pathways. vascular inflammation; NADPH oxidases; cytokines; superoxide; metabolic syndrome Address for reprint requests and other correspondence: K. K. Griendling, Div. of Cardiology, Emory Univ., 319 WMB, 1639 Pierce Dr., Atlanta, GA 30322 (e-mail: kgriend{at}emory.edu )