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.


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.


CONCLUSIONS
SOD2 protects against oxidative stress and endothelial dysfunction in carotid artery of apoE-deficient mice.
Ohashi
Masuo
M
Cardiovascular Center and Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Runge
Marschall S
MS
Faraci
Frank M
FM
Heistad
Donald D
DD
D000818:Animals; D001011:Aorta / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology; D002339:Carotid Arteries / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013482:Superoxide Dismutase / Q000172:deficiency*; D013481:Superoxides / Q000378:metabolism; D017539:Tunica Intima / Q000473:pathology; D014666:Vasomotor System / Q000503:physiopathology
D001057:Apolipoproteins E; D013481:Superoxides; D002784:Cholesterol; D013482:Superoxide Dismutase