OBJECTIVE: To study the effects of heparin on the production of homocysteine-induced extracellular matrix metalloproteinase-2 (MMP-2) in cultured rat vascular smooth muscle cells. METHODS: The effects of different homocysteine levels (0 micromol/L to 1000 micromol/L) on MMP-2 production and the effects of different heparin concentrations (0 microg/mL to 100 microg/mL) on homocysteine-induced MMP-2 in cultured rat vascular smooth muscle cells were examined using gelatin zymography and Western blotting. The changes in MMP-2 were further compared with various treatments for 24 h, 48 h and 72 h. RESULTS: Homocysteine (50 micromol/L to 1000 micromol/L) increased the production of MMP-2 significantly in a dose-dependent manner. Increased production of MMP-2 induced by homocysteine was reduced by the extracellular addition of heparin in a dose-dependent manner. Production of MMP-2 with various treatment regimens for 72 h was greater than for 24 h and 48 h. CONCLUSIONS: Extracellular addition of heparin decreased homocysteine-induced MMP-2 secretion. Data suggest a mechanism by which hyperhomocysteinemia is involved in the pathogenesis of coronary artery disease and demonstrate a beneficial effect of heparin on these conditions.
OBJECTIVE: To study the effects of heparin on the production of homocysteine-induced extracellular matrix metalloproteinase-2 (MMP-2) in cultured rat vascular smooth muscle cells. METHODS: The effects of different homocysteine levels (0 micromol/L to 1000 micromol/L) on MMP-2 production and the effects of different heparin concentrations (0 microg/mL to 100 microg/mL) on homocysteine-induced MMP-2 in cultured rat vascular smooth muscle cells were examined using gelatin zymography and Western blotting. The changes in MMP-2 were further compared with various treatments for 24 h, 48 h and 72 h. RESULTS:Homocysteine (50 micromol/L to 1000 micromol/L) increased the production of MMP-2 significantly in a dose-dependent manner. Increased production of MMP-2 induced by homocysteine was reduced by the extracellular addition of heparin in a dose-dependent manner. Production of MMP-2 with various treatment regimens for 72 h was greater than for 24 h and 48 h. CONCLUSIONS: Extracellular addition of heparin decreased homocysteine-induced MMP-2 secretion. Data suggest a mechanism by which hyperhomocysteinemia is involved in the pathogenesis of coronary artery disease and demonstrate a beneficial effect of heparin on these conditions.
Authors: E G Vermeulen; H W Niessen; M Bogels; C D Stehouwer; J A Rauwerda; V W van Hinsbergh Journal: Arterioscler Thromb Vasc Biol Date: 2001-04 Impact factor: 8.311
Authors: J C Tsai; H Wang; M A Perrella; M Yoshizumi; N E Sibinga; L C Tan; E Haber; T H Chang; R Schlegel; M E Lee Journal: J Clin Invest Date: 1996-01-01 Impact factor: 14.808