ABSTRACT
Homocysteine is an important intermediate product in normal metabolism of methionine. Elevation of homocysteine is known as an independent risk factor for atherosclerosis. On the other hand, several studies have reported beneficial effects of folates on endothelial dysfunction. However, the exact mechanism remains to be elucidated. Thus, the objectives of this study were to assess the relationship between total plasma homocysteine and early atherosclerosis, b] to determine whether homocysteine exerts its effects through the adhesion molecule VCAM-]1 or not, c] To estimate the role of folic acid as a prophylactic and or treatment of early atherosclerotic changes. Adult male mice [n=40,] were randomly divided into 4 groups. Group I received the control diet. Group II received control diet plus methionine dissolved in drinking water, adjusted to deliver a total of 4.4%methionine/L drinking water for 8 weeks and the doses were calculated assuming an average water intake of 3 to 4 mL/d and an average body weight of 25 g. Group III received methionine in the same previous dose and duration concomitant with folic acid in a dose of 1mg/kg. Group IV received methionine in the same previous dose and duration followed by folic acid in the same previous dose for another 8 weeks. Blood samples were taken for estimation of homocysteine, Cholesterol, triglycerides, LDL, HDL, nitric oxide, superoxide dismutase. Specimens from aorta were taken and processed for histopathological and immunohistochemical examination. The high expression of VC'AM4 in group II might be responsible for the observed histological changes; adherent inflammatory cells to the irregular endothelial lining in addition to increased intima-media thickness, formation of intimal foam cells, hyperplastic changes, migration of the smooth muscle cells of the media, increase collagen and disturbed elastic fibers architecture. The plasma homocysteine and cholesterol levels were significantly higher in group II than in group I. It was reduced in group III and IV. Although, there was no significant dfference between their levels in group I and III, there was significant difference between group I and IV LDL, HDL, and triglycerides plasma levels did not differ statistically between different groups. Nitric oxide and superoxide were markedly reduced in group II with improvement in groups III and IV. However, the nitric oxide level in group I was significantly higher than that in group Ill and IV While no significant differences between group I, III and IV in superoxide dismutase levels. As regard the endothelial 'VCAM-1 expression, marked increase in the expression in group II, low expression in group III [similar to control] and moderate expression in group IV were observed. Elevated plasma homocysteine is a risk factor for early atherosclerosis which was confirmed by the endothelial expression of VCAM-1. Prophylactic administration of folic acid has a beneficial effect more than its role as a treatment