Nutritional B vitamin deficiency alters the expression of key proteins associated with vascular smooth muscle cell proliferation and migration in the aorta of atherosclerotic apolipoprotein E null mice.

Duthie, Susan J.; Beattie, John H.; Gordon, Margaret-J.; Pirie, Lynn P.; Nicol, Fergus; Reid, Martin D.; Duncan, Gary J.; Cantlay, Louise; Horgan, Graham; McNeil, Christopher J.

Abstract

Low B vitamin status is linked with human vascular disease. We employed a proteomic and biochemical approach to determine whether nutritional folate deficiency and/or hyperhomocysteinemia altered metabolic processes linked with atherosclerosis in ApoE null mice. Animals were fed either a control fat (C; 4 % w/w lard) or a high-fat [HF; 21 % w/w lard and cholesterol (0/15 % w/w)] diet with different B vitamin compositions for 16 weeks. Aorta tissue was prepared and global protein expression, B vitamin, homocysteine and lipoprotein status measured. Changes in the expression of aorta proteins were detected in response to multiple B vitamin deficiency combined with a high-fat diet (P < 0.05) and were strongly linked with lipoprotein concentrations measured directly in the aorta adventitia (P < 0.001). Pathway analysis revealed treatment effects in the aorta-related primarily to cytoskeletal organisation, smooth muscle cell adhesion and invasiveness (e.g., fibrinogen, moesin, transgelin, vimentin). Combined B vitamin deficiency induced striking quantitative changes in the expression of aorta proteins in atherosclerotic ApoE null mice. Deregulated expression of these proteins is associated with human atherosclerosis. Cellular pathways altered by B vitamin status included cytoskeletal organisation, cell differentiation and migration, oxidative stress and chronic inflammation. These findings provide new insight into the molecular mechanisms through which B vitamin deficiency may accelerate atherosclerosis.

Citation

DUTHIE, S.J., BEATTIE, J.H., GORDON, M.-J., PIRIE, L.P., NICOL, F., REID, M.D., DUNCAN, G.J., CANTLAY, L., HORGAN, G. and MCNEIL, C.J. 2015. Nutritional B vitamin deficiency alters the expression of key proteins associated with vascular smooth muscle cell proliferation and migration in the aorta of atherosclerotic apolipoprotein E null mice. Genes and nutrition [online], 10(1), article 446. Available from: https://doi.org/10.1007/s12263-014-0446-y

• Journal Article Type: Article
• Acceptance Date: Nov 21, 2014
• Online Publication Date: Dec 2, 2014
• Publication Date: Jan 31, 2015
• Deposit Date: Feb 10, 2020
• Publicly Available Date: Feb 10, 2020
• Journal: Genes and nutrition
• Print ISSN: 1555-8932
• Electronic ISSN: 1865-3499
• Publisher: Springer
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 1
• Article Number: 446
• DOI: https://doi.org/10.1007/s12263-014-0446-y
• Keywords: Aorta proteome; ApoE null mice; Atherosclerosis; B vitamins; Hyperhomocysteinemia
• Public URL: https://rgu-repository.worktribe.com/output/828403