Effects of magnesium on the production of extracellular matrix metalloproteinases in cultured rat vascular smooth muscle cells.
The precise correlation between magnesium and cardiovascular disease remains to be established. Matrix metalloproteinases (MMPs) are expressed in coronary arterial atherosclerotic lesions. MMP production in vascular smooth muscle cells (VSMCs) is stimulated by growth factors such as platelet-derived growth factor (PDGF). To assess the association between magnesium and MMPs, we examined the effects of different extracellular magnesium concentrations (0-3.0 mmol/l) on MMPs production in cultured rat VSMCs under basal and PDGF-stimulated conditions using gelatin zymography and western blotting. As magnesium is called a natural calcium antagonist, we further compared the effects of magnesium with some calcium antagonists. Magnesium reduced MMP-2 production dose-dependently at basal and PDGF-stimulated conditions in VSMCs. However, neither verapamil nor nifedipine influenced MMP-2 production under any conditions examined. The effect of magnesium on the production of MMP-2 was inhibited by two tyrosine kinase inhibitors-genistein and herbimycin A. The results of this study indicate that extracellularly added magnesium decreased MMPs secretion, which appears to be associated with protein tyrosine kinase.
Yue
Hong
H
First Department of Internal Medicine, Fukui Medical University, 23-3 Shimoaizuki, Matsuoka-Cho, Fukui 910-1193, Japan.
Lee
Jong-Dae
JD
Shimizu
Hiromasa
H
Uzui
Hiroyasu
H
Mitsuke
Yasuhiko
Y
Ueda
Takanori
T
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008278:Magnesium Sulfate / Q000494:pharmacology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000187:drug effects* / Q000378:metabolism*; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D014700:Verapamil / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor; D008278:Magnesium Sulfate; D014700:Verapamil; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D009543:Nifedipine