Effects of heparin on the production of homocysteine-induced extracellular matrix metalloproteinase-2 in cultured rat vascular smooth muscle cells.
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.
Guo
Hangyuan
H
Department of Cardiology, Shaoxing People's Hospital, The First Affiliated Hospital of Shaoxing University, Shaoxing, China. ghangyuan@hotmail.com
Lee
Jong-Dae
JD
Uzui
Hiroyasu
H
Yue
Hong
H
Wang
Ping
P
Toyoda
Kiyohiro
K
Geshi
Tooru
T
Ueda
Takanori
T
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001011:Aorta; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D006710:Homocysteine / Q000009:adverse effects* / Q000378:metabolism; D066298:In Vitro Techniques; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000925:Anticoagulants; D006710:Homocysteine; D006493:Heparin; D020778:Matrix Metalloproteinase 2