Effects of rosuvastatin on the production and activation of matrix metalloproteinase-2 and migration of cultured rat vascular smooth muscle cells induced by homocysteine

Objective: To test the influence of homocysteine on the production and activation of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase-2 (TIMP-2) and on cell migration of cultured rat vascular smooth muscle cells (VSMCs). Also, to explore whether rosuvastatin can alter the abnormal secretion and activation of MMP-2 and TIMP-2 and migration of VSMCs induced by homocysteine. Methods: Rat VSMCs were incubated with different concentrations of homocysteine (50–5 000 μmol/L). Western blotting and gelatin zymography were used to investigate the expressions and activities of MMP-2 and TIMP-2 in VSMCs in culture medium when induced with homocysteine for 24, 48, and 72 h. Transwell chambers were employed to test the migratory ability of VSMCs when incubated with homocysteine for 48 h. Different concentrations of rosuvastatin (10⁻⁹–10⁻⁵ mol/L) were added when VSMCs were induced with 1 000 μmol/L homocysteine. The expressions and activities of MMP-2 and TIMP-2 were examined after incubating for 24, 48, and 72 h, and the migration of VSMCs was also examined after incubating for 48 h. Results: Homocysteine (50–1 000 μmol/L) increased the production and activation of MMP-2 and expression of TIMP-2 in a dose-dependent manner. However, when incubated with 5 000 μmol/L homocysteine, the expression of MMP-2 was up-regulated, but its activity was down-regulated. Increased homocysteine-induced production and activation of MMP-2 were reduced by rosuvastatin in a dose-dependent manner whereas secretion of TIMP-2 was not significantly altered by rosuvastatin. Homocysteine (50–5 000 μmol/L) stimulated the migration of VSMCs in a dose-dependent manner, but this effect was eliminated by rosuvastatin. Conclusions: Homocysteine (50–1 000 μmol/L) significantly increased the production and activation of MMP-2, the expression of TIMP-2, and the migration of VSMCs in a dose-dependent manner. Additional extracellular rosuvastatin can decrease the excessive expression and activation of MMP-2 and abnormal migration of VSMCs induced by homocysteine.     

CD_(40)-CD_(40)L相互作用对人脐静脉内皮细胞增殖及迁移的影响

目的探讨CD40-CD40配体相互作用对体外培养的人脐静脉内皮细胞(HUVEC)增殖及迁移的影响。方法采用Ⅱ型胶原酶消化法培养人脐静脉内皮细胞,以3H-胸腺嘧啶脱氧核苷(3H-TdR)、3H-亮氨酸(3H-Leu)掺入法分别测定HUVEC增殖,内皮细胞的迁移采用琼脂糖凝胶刮取法,倒置显微镜观察。结果CD40-CD40配体相互作用能明显促进HUVEC3H-TdR、3H-Leu的掺入,两者具有时间、剂量依赖性,CD40-CD40配体相互作用随CD40L浓度的增加及刺激时间延长(30h内),能明显增加内皮细胞迁移率,an-ti-CD40单克隆抗体能明显抑制上述效应。结论CD40-CD40配体相互作用能促进内皮细胞增殖、迁移。