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En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries
Published on: February 25, 2016
MnSOD deficiency increases endothelial dysfunction in ApoE-deficient mice
Masuo Ohashi1, Marschall S Runge, Frank M Faraci
1Cardiovascular Center and Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
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.
Conclusions:
SOD2 protects against oxidative stress and endothelial dysfunction in carotid artery of apoE-deficient mice.
Insights
Mitochondrial superoxide dismutase (SOD2) protects against vascular oxidative stress and endothelial dysfunction in mice lacking apolipoprotein E (apoE). This highlights SOD2's role in preventing atherosclerosis progression.
Area of Science:
- Cardiovascular Biology
- Mitochondrial Medicine
- Atherosclerosis Research
Background:
- Mice heterozygous for mitochondrial superoxide dismutase (SOD2(+/-)) and deficient in apolipoprotein E (apoE(-/-)) exhibit increased mitochondrial DNA damage and atherosclerotic lesion formation.
- Oxidative stress, particularly from superoxide radicals, is implicated in the pathogenesis of atherosclerosis.
Purpose of the Study:
- To investigate the protective role of SOD2 against elevated vascular superoxide and endothelial dysfunction in apoE-deficient mice.
- To determine if SOD2 deficiency exacerbates atherosclerosis in the context of apoE deficiency.
Main Methods:
- Four groups of mice were studied: apoE(-/-)/SOD2(+/-), apoE(-/-)/SOD2(+/+), apoE(+/+)/SOD2(+/-), and apoE(+/+)/SOD2(+/+).
- Mice were fed a normal chow diet and assessed at 15-17 months of age.
- Vascular superoxide levels and endothelial function (acetylcholine-induced relaxation) were measured in the carotid artery and aorta.
Main Results:
- Serum cholesterol levels were comparable between relevant mouse groups.
- Increased intimal area was observed in the aorta of apoE-deficient mice, regardless of SOD2 status.
- Carotid arteries of apoE(-/-)/SOD2(+/-) mice showed significantly higher superoxide levels and impaired acetylcholine-induced relaxation compared to apoE(-/-)/SOD2(+/+) mice.
- Aorta of apoE-deficient mice exhibited increased superoxide and impaired relaxation, with similar responses between SOD2 genotypes.
Conclusions:
- SOD2 plays a protective role against oxidative stress and endothelial dysfunction in the carotid artery of apoE-deficient mice.
- These findings underscore the importance of mitochondrial antioxidant defense in preventing vascular complications associated with atherosclerosis.
