Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 361-368 |
| Number of pages | 8 |
| Journal | Clinical Epigenetics |
| Volume | 2 |
| Issue number | 2 |
| Early online date | 20 Feb 2011 |
| DOIs | |
| Publication status | Published - 1 Aug 2011 |
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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 journal › Article
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TY - JOUR
T1 - 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
AU - McNeil, Chris J.
AU - Beattie, John H.
AU - Gordon, M .J.
AU - Pirie, Lynn P.
AU - Duthie, Susan J.
PY - 2011/8/1
Y1 - 2011/8/1
N2 - 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.
AB - 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.
KW - folic acid and B-vitamin deficiency in ApoE null mice
KW - atherosclerosis
KW - aortic plaques
KW - hyperhomocysteinemia
KW - genome-wide DNA methylation
KW - vascular tissue
U2 - 10.1007/s13148-011-0022-x
DO - 10.1007/s13148-011-0022-x
M3 - Article
VL - 2
SP - 361
EP - 368
JO - Clinical Epigenetics
JF - Clinical Epigenetics
SN - 1868-7075
IS - 2
ER -