Mild methionine excess does not affect thymidylate synthesis or inflammation markers expression in human aortic endothelial cells.
BACKGROUND
Recent studies in animal models have shown that high methionine intakes induce atherosclerotic changes that may be exacerbated when deficiencies of vitamins B(6), B(12) and folate are present. However, the mechanism underlying this possible atherogenic effect remains unknown. The aim of the present study was to evaluate the effects of methionine on the folate-dependent thymidylate-DNA synthesis, as a possible mechanism of atherogenicity, as well as the effect of high methionine/low folate on several key inflammation markers, such as vascular cell adhesion molecule-1 (VCAM-1), receptor for advanced glycation end products (RAGE) and matrix metalloproteinase-9 (MMP-9) in human aortic endothelial cells.


METHODS
Deoxyuridine suppression test was performed in order to evaluate thymidylate synthesis. To examine the expression of inflammation markers, cells were exposed to high methionine/low folate media for 9 days.


RESULTS
The assayed methionine levels (0.1, 0.5 and 5 mM) did not affect the de novo thymidylate-DNA synthesis. Consistent with this result, methionine (1 and 2.5 mM), alone or in combination with folate deficiency, increased homocysteine levels but did not induce the expression of the inflammation markers evaluated.


CONCLUSIONS
Under the study conditions, methionine was not able to exert the atherogenic mechanism proposed and did not have the hypothesized inflammatory consequences in human aortic endothelial cells.
Achón
María
M
Departamento Nutrición, Bromatología y Tecnología de los Alimentos, Facultad de Farmacia, Universidad San Pablo-CEU, Madrid, Spain. achontu@ceu.es
Alonso-Aperte
Elena
E
Varela-Moreiras
Gregorio
G
Selhub
Jacob
J
D001011:Aorta / Q000166:cytology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism*; D005494:Folic Acid Deficiency / Q000150:complications; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006710:Homocysteine / Q000097:blood; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008715:Methionine / Q000008:administration & dosage*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D013938:Thymidine Monophosphate / Q000096:biosynthesis*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D017127:Glycation End Products, Advanced; D018836:Inflammation Mediators; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D019010:Vascular Cell Adhesion Molecule-1; D006710:Homocysteine; D013938:Thymidine Monophosphate; D008715:Methionine; D020780:Matrix Metalloproteinase 9