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

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.

Folic acid depletion as well as oversupplementation helps in the progression of hepatocarcinogenesis in HepG2 cells

“…A study by Xirong et al, confirmed high expression of DPT in the fully developed liver and fetal life, while it decreased in HCC tissues 49 . Reduced DPT mRNA in our experiments was in concordance with findings in ApoE null mice, in which feeding mice with a combination of folate deficiency and a fat rich diet decreased DPT expression, which regulate differentiation, adhesion and migration abilities of the cell 50 . It is also among the top up-regulated genes in severe NAFLD 51 , NASH and fibrosis 52 .…”

Interaction of genotype and diet on small intestine microbiota of Japanese quail fed a cholesterol enriched diet

“…Complex sphingolipids are essential structural components of intestinal membranes, providing protection and integrity to the intestinal mucosa and regulating intestinal absorption processes. The role of sphingolipid signaling has been established in numerous cellular events, including intestinal cell survival, growth, differentiation, and apoptosis 68 , 69 . An important biochemical change associated with vitamin B6 deficiency is that of hyperhomocysteinemia which was recognized as a cardiovascular event risk factor 67 .…”