Aortic wall damage in mice unable to synthesize ascorbic acid
Open accessAbstract
By inactivating the gene for l -gulono-γ-lactone oxidase, a key enzyme in ascorbic acid synthesis, we have generated mice that, like humans, depend on dietary vitamin C. Regular chow, containing about 110 mg/kg of vitamin C, is unable to support the growth of the mutant mice, which require l -ascorbic acid supplemented in their drinking water (330 mg/liter). Upon withdrawal of supplementation, plasma and tissue ascorbic acid levels decreased to 10–15% of normal within 2 weeks, and after 5 weeks the mutants became anemic, began to lose weight, and die. Plasma total antioxidative capacities were approximately 37% normal in homozygotes after feeding the unsupplemented diet for 3–5 weeks. As plasma ascorbic acid decreased, small, but significant, increases in total cholesterol and decreases in high density lipoprotein cholesterol were observed. The most striking effects of the marginal dietary vitamin C were alterations in the wall of aorta, evidenced by the disruption of elastic laminae, smooth muscle cell proliferation, and focal endothelial desquamation of the luminal surface. Thus, marginal vitamin C deficiency affects the vascular integrity of mice unable to synthesize ascorbic acid, with potentially profound effects on the pathogenesis of vascular diseases. Breeding the vitamin C-dependent mice with mice carrying defined genetic mutations will provide numerous opportunities for systematic studies of the role of antioxidants in health and disease.
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Vitamin C has the ability to prevent LDL oxidation and consequently slows down the peroxidation of lipids.
“Vitamin C has the ability to prevent LDL oxidation and consequently slows down the peroxidation of lipids (Maeda et al. 2000).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Maeda et al. 2000
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“033 g/L) in the drinking water, which prevents scurvy in adult Gulo mice but does not allow the ascorbate levels in the plasma to reach that of Gulo mice (37).”
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- Authors
- Maeda, N., Hagihara, H., Nakata, Y., Hiller, S., Wilder, J., & Reddick, R.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-01-18
- Volume
- 97
- Issue
- 2
- Pages
- 841-846
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC15418
- OpenAlex
- W1997409763
- Cited by
- 260
- References
- 36
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 17 · 2023: 8 · 2022: 12 · 2021: 8 · 2020: 14 · 2019: 11 · 2018: 10 · 2017: 12 · 2016: 8 · 2015: 11 · 2014: 10 · 2013: 24 · 2012: 18
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- American Heart Association
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL 42630, R37HL042630, R01HL042630)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- scurvy, ascorbic acid biosynthesis, elastic lamina, smooth muscle cell proliferation, endothelial desquamation, plasma antioxidant capacity, total cholesterol, HDL cholesterol, vascular integrity, antioxidants
- MeSH terms
- Animals, Antioxidants, Aorta, Thoracic, Ascorbic Acid, Ascorbic Acid Deficiency, Cell Division, Cholesterol, Diet, Elastic Tissue, Female, Genotype, Homozygote, Cholesterol, HDL, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Microscopy, Electron, Muscle, Smooth, Vascular, Sugar Alcohol Dehydrogenases, Mutagenesis, Site-Directed, L-Gulonolactone Oxidase, Mice, Rats
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