MnSOD deficiency increases endothelial dysfunction in ApoE-deficient mice

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

doi:10.1161/01.ATV.0000238347.77590.c9

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MnSOD deficiency increases endothelial dysfunction in ApoE-deficient mice

Journal article

Open access

Peer reviewed

MnSOD deficiency increases endothelial dysfunction in ApoE-deficient mice

Masuo Ohashi, Marschall S Runge, Frank M Faraci and Donald D Heistad

Arteriosclerosis, thrombosis, and vascular biology, Vol.26(10), pp.2331-2336

10/2006

DOI: 10.1161/01.ATV.0000238347.77590.c9

PMID: 16873728

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Abstract

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

Carotid Arteries - metabolism

Atherosclerosis - pathology

Apolipoproteins E - deficiency

Cholesterol - blood

Mice, Inbred C57BL

Endothelium, Vascular - physiopathology

Superoxide Dismutase - deficiency

Aorta - metabolism

Endothelium, Vascular - enzymology

Mice, Knockout

Aorta - pathology

Atherosclerosis - etiology

Animals

Tunica Intima - pathology

Carotid Arteries - physiopathology

Vasomotor System - physiopathology

Superoxides - metabolism

Carotid Arteries - enzymology

Carotid Arteries - pathology

Mice

Aorta - physiopathology

Aorta - enzymology

Details

Title: Subtitle: MnSOD deficiency increases endothelial dysfunction in ApoE-deficient mice
Creators: Masuo Ohashi - Cardiovascular Center and Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Marschall S Runge
Frank M Faraci
Donald D Heistad
Resource Type: Journal article
Publication Details: Arteriosclerosis, thrombosis, and vascular biology, Vol.26(10), pp.2331-2336
DOI: 10.1161/01.ATV.0000238347.77590.c9
PMID: 16873728
NLM abbreviation: Arterioscler Thromb Vasc Biol
ISSN: 1079-5642
eISSN: 1524-4636
Publisher: United States
Grant note: DK 54759 / NIDDK NIH HHS DK 52617 / NIDDK NIH HHS HL 55006 / NHLBI NIH HHS NS 24621 / NINDS NIH HHS HL 14388 / NHLBI NIH HHS DK 15843 / NIDDK NIH HHS HL 62984 / NHLBI NIH HHS HL 16066 / NHLBI NIH HHS HL 38901 / NHLBI NIH HHS
Language: English
Date published: 10/2006
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040243202771

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