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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
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Aortic wall damage in mice unable to synthesize ascorbic acid.

N Maeda1, H Hagihara, Y Nakata

  • 1Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA. nobuyo@med.unc.edu

Proceedings of the National Academy of Sciences of the United States of America
|January 19, 2000
PubMed
Summary

Mice engineered to lack vitamin C synthesis exhibit scurvy-like symptoms and vascular damage when deprived of dietary ascorbic acid. This model is crucial for studying vitamin C deficiency and its impact on vascular health.

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Area of Science:

  • Biochemistry
  • Genetics
  • Physiology

Background:

  • Humans and guinea pigs are among the few mammals unable to synthesize ascorbic acid (vitamin C) due to the lack of the L-gulono-gamma-lactone oxidase enzyme.
  • Understanding the physiological roles of vitamin C is essential for human health, particularly in preventing deficiency diseases like scurvy.

Purpose of the Study:

  • To generate and characterize a mouse model deficient in vitamin C synthesis, mimicking human dietary requirements.
  • To investigate the physiological and pathological consequences of marginal vitamin C deficiency in vivo.

Main Methods:

  • Inactivation of the L-gulono-gamma-lactone oxidase gene in mice to create vitamin C dependency.
  • Administration of vitamin C-supplemented or unsupplemented diets and drinking water.
  • Monitoring of plasma and tissue ascorbic acid levels, hematological parameters, lipid profiles, and aortic tissue integrity.

Main Results:

  • Mutant mice require dietary ascorbic acid supplementation for survival and normal growth.
  • Vitamin C withdrawal led to decreased ascorbic acid levels, anemia, weight loss, and mortality.
  • Marginal vitamin C deficiency resulted in altered plasma lipid profiles and significant aortic wall damage, including disrupted elastic laminae and smooth muscle cell proliferation.

Conclusions:

  • The generated mouse model effectively mimics human vitamin C dependency and deficiency symptoms.
  • Marginal vitamin C deficiency profoundly impacts vascular integrity, suggesting a role in the pathogenesis of vascular diseases.
  • This model offers a valuable platform for future research into the role of antioxidants in health and disease.