MnSOD Deficiency Increases Endothelial Dysfunction in ApoE-Deficient Mice

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 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.