Role of dietary supplementation of methionine and Folic acid in early atherosclerotic Changes in adult male mice

Background: Homocysteine (Hcy) is an important intermediate product in normal
metabolism of methionine. On the other hand, several studies have reported
beneficial effects of folate on endothelial dysfunction. However the exact mechanism
remains to be elucidated. Thus the objective of this study was to asses the relationship
between total plasma Homocysteine (tHcy) and early atherosclerotic changes and
whether Hcy exerts its effect through the vascular adhesion molecule (VCAM-1) or
not. Study Design: Forty adult male mice were randomly divided into 4 groups, each
group included 10 mice. Control group which received the control diet. Group II:
which received the control diet plus methionine dissolved in drinking water (4.4%) at
doses of 3-4 ml/day/mice for 8 weeks. Group III: received the control diet and
methionine by the same previous dose and duration, concomitant with folic acid in a
dose 1mg/kg. Group IV: received the control diet and methionine by the same
previous dose and duration then followed by folic acid in the same previous dose for
another 8 weeks. Blood samples were taken for estimation of tHcy ,total cholesterol
(TC),High density lipoprotien (HDL),Low density lipoprotein (LDL), nitric oxide
(NO) , superoxide dismutase (SOD) . Specimens from aorta were taken and processed
for imunohistochemical staining of VCAM-1 and histopathological examination.
Results: The plasma level of Hcy and cholesterol of group II were significantly higher
than those of the remaining groups and there was a positive correlation between
plasma level of Hcy and cholesterol. Although there was no significant difference
between group I and group III ,there was a significant difference of these levels
between group I and group IV. Plasma levels of LDL,HDL and triglycerides did not
differ statistically between all studied groups. Plasma levels of NO in group II was
significantly lower than the other studied group .Its levels in group I was significantly
higher than that ofgroup III and group IV. Plasma levels of SOD of group II was
significantly lower than the other studiedgroup. Although there was no significant
difference between NO levels of group I and group III, there was a significant
difference of these levels between group I and group IV. As regard the endothelial
VCAM-1 expression, marked increase in the expression of VCAM-1 in group II. Low
expression in group III (similar to the groupI). Moderate expression of group IV. The
high expression of VCAM-1 in group II might be responsible for the observed
histological changes; thickening of the aortic wall and adherent inflammatory cells to
the irregular endothelial lining. Conclusion:Elevated plasma homocysteine is a risk
factor for early atherosclerosis which was confirmed by the endothelial expression of
VCAM-1. Prophylactic administration of folicacid has a beneficial effect more than
its role as a treatment