title: Vulnerable atherosclerotic plaque morphology in apolipoprotein E-deficient mice unable to make ascorbic Acid.
abstract: BACKGROUND
  Oxidative stress is thought to play an important role in atherogenesis, suggesting that antioxidants could prevent coronary artery disease. However, the efficacy of vitamin C in reducing atherosclerosis is debatable in humans and has not been tested rigorously in animals.
  
  
  RESULTS
  Gulo(-/-)Apoe(-/-) mice were used to test a hypothesis that chronic vitamin C deficiency enhances the initiation and development of atherosclerosis. These mice are dependent on dietary vitamin C because of the lack of L-gulonolactone-gamma-oxidase and are prone to develop atherosclerosis because of lacking apolipoprotein E. Beginning at 6 weeks of age, the Gulo(-/-)Apoe(-/-) mice were fed regular chow or Western-type diets containing high fat and supplemented with either 0.033 g or 3.3 g/L of vitamin C in their drinking water. This regimen produced mice with chronically low vitamin C (average 1.5 microg/mL in plasma) or high vitamin C (average 10 to 30 microg/mL in plasma). Morphometric analysis showed that within each sex, age, and diet group, the sizes of the atherosclerotic plaques were not different between low vitamin C mice and high vitamin C mice. However, advanced plaques in the low vitamin C mice had significantly reduced amounts of Sirius red-staining collagen (36.4+/-2.2% versus 54.8+/-2.3%, P<0.0001), larger necrotic cores within the plaques, and reduced fibroproliferation and neovascularization in the aortic adventitia.
  
  
  CONCLUSIONS
  Chronic vitamin C deficiency does not influence the initiation or progression of atherosclerotic plaques but severely compromises collagen deposition and induces a type of plaque morphology that is potentially vulnerable to rupture.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599-7125, USA.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakata
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D001205:Ascorbic Acid / Q000235:genetics* / Q000378:metabolism; D001206:Ascorbic Acid Deficiency / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D001786:Blood Glucose; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003094:Collagen / Q000378:metabolism; D003433:Crosses, Genetic; D004041:Dietary Fats; D019587:Dietary Supplements; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D050544:L-Gulonolactone Oxidase; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012737:Sex Factors; D013401:Sugar Alcohol Dehydrogenases / Q000172:deficiency / Q000235:genetics; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D008076:Cholesterol, HDL; D004041:Dietary Fats; D014280:Triglycerides; D003094:Collagen; D002784:Cholesterol; D013401:Sugar Alcohol Dehydrogenases; D050544:L-Gulonolactone Oxidase; D001205:Ascorbic Acid