Differential effects of nutritional folic acid deficiency and moderate hyperhomocysteinemia on aortic plaque formation and genome-wide DNA methylation in vascular tissue from ApoE -/- mice

Chris J. McNeil, John H. Beattie, M .J. Gordon, Lynn P. Pirie, Susan J. Duthie

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Low folate intake is associated with vascular disease. Causality has been attributed to hyperhomocysteinemia. However, human intervention trials have failed to show the benefit of homocysteine-lowering therapies. Alternatively, low folate may promote vascular disease by deregulating DNA methylation. We investigated whether folate could alter DNA methylation and atherosclerosis in ApoE null mice. Mice were fed one of six diets (n¿=¿20 per group) for 16 weeks. Basal diets were either control (C; 4% lard) or high fat (HF; 21% lard and cholesterol, 0.15%) with different B-vitamin compositions: (1) folic acid and B-vitamin replete, (2) folic acid deficient (-F), (3) folic acid, B6 and B12 deficient (-F-B). -F diets decreased plasma (up to 85%; P¿<¿0.05), whole blood (up to 70%; P¿<¿0.05), and liver folate (up to 65%; P¿<¿0.05) and hepatic SAM/SAH (up to 80%; P¿<¿0.05). -F-B diets reduced plasma (up to 76%; P¿<¿0.05), whole blood (up to 72%; P¿<¿0.05), and liver B12 (up to 39%; P¿<¿0.05) and hepatic SAM/SAH (up to 90%; P¿<¿0.05). -F increased homocysteine 2-fold, while -F-B increased homocysteine 3.6- and 6.8-fold in the C and HF groups (P¿<¿0.05). Plaque formation was increased 2-fold (P¿<¿0.0001) in mice fed a HF diet. Feeding a HF–F diet increased lesion formation by 17% (P¿<¿0.05). There was no change in 5-methyldeoxycytidine in liver or vascular tissue (aorta, periadventitial tissue and heart). These data suggest that atherogenesis is not associated with genome-wide epigenetic changes in this animal model.
Original languageEnglish
Pages (from-to)361-368
Number of pages8
JournalClinical Epigenetics
Volume2
Issue number2
Early online date20 Feb 2011
DOIs
Publication statusPublished - 1 Aug 2011

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Folic Acid Deficiency
Hyperhomocysteinemia
Apolipoproteins E
DNA Methylation
Folic Acid
Blood Vessels
Genome
Diet
Homocysteine
Liver
5-methyldeoxycytidine
Vascular Diseases
Atherosclerosis
Riboflavin
Thiamine
Epigenomics
Causality
Aorta
Animal Models
Fats

Keywords

  • folic acid and B-vitamin deficiency in ApoE null mice
  • atherosclerosis
  • aortic plaques
  • hyperhomocysteinemia
  • genome-wide DNA methylation
  • vascular tissue

Cite this

Differential effects of nutritional folic acid deficiency and moderate hyperhomocysteinemia on aortic plaque formation and genome-wide DNA methylation in vascular tissue from ApoE -/- mice. / McNeil, Chris J.; Beattie, John H.; Gordon, M .J.; Pirie, Lynn P.; Duthie, Susan J.

In: Clinical Epigenetics, Vol. 2, No. 2, 01.08.2011, p. 361-368.

Research output: Contribution to journalArticle

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AU - Duthie, Susan J.

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