Lack of effect of diet-induced hypomethylation on endothelium-dependent relaxation in rats

Hirsch, S; Ronco, AM; Pinardi, G; Montequin, MJ; Leiva, L; de la Maza, MP; Llanos, M; Bunout, D

Abstract

Background: Endothelial dysfunction is a key process in atherosclerosis. Hypomethylation is one of the postulated mechanisms involved in atherogenesis and is mainly secondary to a decrease in essential factors such as, folate and vitamin B12 for the biosynthesis of S-adenosylmethionine (SAM), the main methyl-group donor for methylation reactions. Aim: To investigate in an animal model, whether hypomethylation, secondary to folate or vitamin B12 deficiency, affects endothelium-dependent relaxation (EDR) induced by acetylcholine (ACh). Methods: Adult male Wistar rats were divided into 4 groups of 12 rats each: folate and B12 deficiency (FB12D 0 mg folate/kg, 0 μg/kg B12), folate deficiency (FD 0 mg folate/kg and 50 μg/kg B12), B12 deficiency (B12D: 8 mg/kg folate and 0 μg/kg B12 and control diet (CD)). After eight weeks the animals were killed and thoracic aorta and liver removed. Serum concentration of homocysteine, folate and vitamin B12 were determined. Hepatic levels of SAM and S-adenosylhomocysteine (SAH) were measured, as indicator of hypomethylation. ACh-induced EDR and sodium nitroprusside (SNP)-induced endothelium-independent relaxation (EIR), in isolated aorta rings were evaluated. Results: Hcy concentrations were significantly increased in the folate and B12 deficient groups. SAM and the SAM/SAH ratio were lower in the FD and FB12D than in the control and B12D group. Folate, B12 deficiency, serum Hcy levels and hepatic SAM/SAH ratio did not affect EDR neither EIR. Conclusions: In adult Wistar rats, chronic folate or folate plus vitamin B12 deficiency generates hypomethylation which is not related to an alteration of endothelial function. © 2008 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.

Más información

Título según WOS: Lack of effect of diet-induced hypomethylation on endothelium-dependent relaxation in rats
Título según SCOPUS: Lack of effect of diet-induced hypomethylation on endothelium-dependent relaxation in rats
Título de la Revista: CLINICAL NUTRITION
Volumen: 27
Número: 6
Editorial: Churchill Livingstone
Fecha de publicación: 2008
Página de inicio: 895
Página final: 899
Idioma: English
URL: http://linkinghub.elsevier.com/retrieve/pii/S0261561408001556
DOI:

10.1016/j.clnu.2008.08.010

Notas: ISI, SCOPUS