Effects of folic acid and magnesium on the production of homocysteine-induced extracellular matrix metallopiroteinase-2 in cultured rat vascular smooth muscle cells

Background Hyperhomocysteinemia is an independent risk factor of coronary artery disease, but some studies have shown that patients with hyperhomocysteinemia are not prone to atherosclerosis. The aim of this study was to test whether homocysteine increases the production of matrix metalloproteinase-2 (MMP-2) and if extracellular additional magnesium and folic acid alters MMP-2 secretion. Methods and Results Gelatin zymography and western blotting were used to investigate the effects of different homocysteine levels (0-5,000 mu mol/L) on MMP-2 production, and the effects of different folic acid concentrations (0-10 mu mol/L) and magnesium concentrations (0-3.0 mmol/L) on homocysteine-induced MMP-2 in cultured rat vascular smooth muscle cells. Furthermore, the changes in MMP-2 were compared under various treatments for 24 h, 48 h and 72 h. Homocysteine (50-1,000 mu mol/L) increased the production of MMP-2 significantly in a dose-dependent manner and at a high level (5,000 mu mol/L) reduced the production of MMP-2. Increased production of MMP-2 induced by homocysteine was reduced by additional extracellular folic acid in a dose-dependent manner. Magnesium also reduced the increase of MMP-2 production induced by homocysteine. Production of MMP-2 under various treatments for 72 h increased more than during 24 or 48 h. Conclusions Homocysteine (50-1,000 mu mol/L) significantly increased the production of MMP-2 in a dose-dependent manner. Added extracellular folic acid and magnesium decreased the homocysteine-induced MMP-2 secretion. These data suggest a beneficial effect of folic acid and magnesium on the pathogenesis of coronary artery disease.