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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2331.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

MnSOD Deficiency Increases Endothelial Dysfunction in ApoE-Deficient Mice

Masuo Ohashi; Marschall S. Runge; Frank M. Faraci; Donald D. Heistad

From the Cardiovascular Center and Department of Internal Medicine and Pharmacology, Roy J. and Lucille A. Carver College of Medicine (M.O., F.M.F., D.D.H.) and VA Medical Center (D.D.H.), The University of Iowa, Iowa City; and the Department of Internal Medicine, University of North Carolina at Chapel Hill (M.S.R.).

Correspondence to Donald D. Heistad, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242. E-mail donald-heistad{at}uiowa.edu

Objective— In mice that are heterozygous for mitochondrial superoxide dismutase (SOD2^+/–) with apoE deficiency (apoE^–/–), mitochondrial DNA damage increases formation of atherosclerotic lesions. The purpose of this study was to determine whether SOD2 provides protection against increased vascular superoxide and endothelial dysfunction in apoE-deficient mice.

Methods and Results— Four groups of mice [apoE^–/–/SOD2^+/– (apoe/sod2), apoE^–/–/SOD2^+/+ (apoe/SOD2), apoE^+/+/SOD2^+/– (apoE/sod2), and apoE^+/+/SOD2^+/+ (apoE/SOD2)] were fed normal chow diet, and studied at 15 to 17 months of age. Serum cholesterol levels were similar in apoe/sod2 and apoe/SOD2 mice, and also were similar in apoE/sod2 and apoE/SOD2 mice. Intimal area was increased in aorta, but not carotid artery, of apoe/sod2 and apoe/SOD2 mice. In carotid artery, superoxide was increased (67±5.2 relative fluorescence intensity/vessel area [RI] in apoe/sod2 mice, 31±3.1 RI in apoE/SOD2 mice, P<0.05), and relaxation to acetylcholine was impaired in apoe/sod2 mice versus apoe/ SOD2, apoE/sod2, apoE/SOD2 mice. Tiron improved relaxation to acetylcholine. In aorta, superoxide levels were increased and relaxation to acetylcholine was impaired in apoe/sod2 and apoe/SOD2 mice, but responses were similar in apoe/sod2 and apoe/SOD2 mice.

Conclusion— SOD2 protects against oxidative stress and endothelial dysfunction in carotid artery of apoE-deficient mice.

The purpose of this study was to determine whether SOD2 provides protection against increased vascular superoxide and endothelial dysfunction in apoE-deficient mice. Superoxide was increased and relaxation to acetylcholine was impaired more in carotid artery of apoE^–/–SOD2^+/– mice than apoE^–/–SOD2^+/+ mice. These findings indicate that SOD2 protects against oxidative stress and endothelial dysfunction in atherosclerosis.

Key Words: MnSOD • apoE • endothelial • superoxide • carotid artery

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