Effect of melatonin on the increased expression of aortic VCAM-1 in the experimental hyperhomocysteinemia

Currently hyperhomocysteinemia is accepted as an important risk factor for cardiovascular and cerebrovascular diseases. Several mechanisms were postulated for homocystein dependent atherosclerosis. However exact moleculer mechanism is not still known. VCAM-1 is endothelial adhesion molecule of immunoglobulin gene super-family and it induces monocyte aggregation in the internal membranes of the arteries. Melatonine is major hormone of the pineal gland and it has protective effect on vascular system by partial inhibition of the expression of adhesion molecules and resultant inhibition of neutrophyl mediated cell injury.Thirty male Wistar albino rats were divided into 3 groups; control (C), homocystein (hcy) homocystein+melatonine (hcy+mel) for the effect of melatonine administration on VCAM-1 adhesion molecule expression in hyperhomocysteinemic rats. Serum homocystein levels were 3,07±0,09 µmol/L in control group, 11,00±0,51 µmol/L in methionine feeded group and 4,01 ± 0,24 µmol/L in concamittant methionine feeded and melatonine supplied rats. Mild (+) VCAM-1 expression was observed in control and hcy+mel groups rat endothelium where as severe (+++) expression was observed in hcy group. Melatonine administration was decreased the VCAM-1 expression by lowering the blood homocystein levels.In conclusion it was thought that increased VCAM-1 expression in hyperhomocysteinemia might be responsible for adhesion of monocytes to endothelial wall. We can say that homocysteine may cause atherogenesis and VCAM-1 expression causes leukocyte migration and activation by increasing the inflammatory response according to our findings. Beside this, melatonine was significantly deppressed the aortic VCAM-1 expression parallel to decrease in blood homocysteine levels. We think that these are due to anti-inflammatory effects of melatonine including chemocine induced mechanisms and these effects may be useful in atherosclerotic patients.Key words: hyperhomocysteinemia, atherosclerosis, VCAM-1, melatonine