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.
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| http://dx.doi.org/10.1016/s0828-282x(07)70754-7 | DOI Listing |
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