Reactive oxygen species-selective regulation of aortic inflammatory gene expression in Type 2 diabetes.
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.
San Martín
Alejandra
A
Division of Cardiology, Department of Medicine, Emory University, 1639 Pierce Dr., Atlanta, GA 30322, USA.
Du
Pingfeng
P
Dikalova
Anna
A
Lassègue
Bernard
B
Aleman
María
M
Góngora
María Carolina
MC
Brown
Kathryn
K
Joseph
Giji
G
Harrison
David G
DG
Taylor
W Robert
WR
Jo
Hanjoong
H
Griendling
Kathy K
KK
D000818:Animals; D001011:Aorta / Q000276:immunology*; D001025:Aortitis / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D007155:Immunologic Factors / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D017382:Reactive Oxygen Species / Q000276:immunology*
D007155:Immunologic Factors; D017382:Reactive Oxygen Species