Effects of Folic Acid and Magnesium on the Production of Homocysteine-Induced Extracellular Matrix Metalloproteinase-2 in Cultured Rat Vascular Smooth Muscle Cells

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概要

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• Background Hyperhomocysteinemia is an independent risk factor of coronary artery disease, but some studies have shown that patients with hyperhomocysteinemia are not prone to atherosclerosis. The aim of this study was to test whether homocysteine increases the production of matrix metalloproteinase-2 (MMP-2) and if extracellular additional magnesium and folic acid alters MMP-2 secretion. Methods and Results Gelatin zymography and western blotting were used to investigate the effects of different homocysteine levels (0-5, 000μmol/L) on MMP-2 production, and the effects of different folic acid concentrations (0-10μmol/L) and magnesium concentrations (0-3.0 mmol/L) on homocysteine-induced MMP-2 in cultured rat vascular smooth muscle cells. Furthermore, the changes in MMP-2 were compared under various treatments for 24 h, 48 h and 72 h. Homocysteine (50-1, 000μmol/L) increased the production of MMP-2 significantly in a dose-dependent manner and at a high level (5, 000μmol/L) reduced the production of MMP-2. Increased production of MMP-2 induced by homocysteine was reduced by additional extracellular folic acid in a dose-dependent manner. Magnesium also reduced the increase of MMP-2 production induced by homocysteine. Production of MMP-2 under various treatments for 72 h increased more than during 24 or 48 h. Conclusions Homocysteine (50-1, 000μmol/L) significantly increased the production of MMP-2 in a dose-dependent manner. Added extracellular folic acid and magnesium decreased the homocysteine-induced MMP-2 secretion. These data suggest a beneficial effect of folic acid and magnesium on the pathogenesis of coronary artery disease.

• 社団法人日本循環器学会の論文
• 2005-12-20

著者

• UZUI Hiroyasu

  First Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui

• UEDA Takanori

  First Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui

• LEE Jong-Dae

  First Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui

• Lee Jong-dae

  京都大学 医学研究科循環器内科学

• Lee Jong-dae

  First Department Of Internal Medicine Faculty Of Medical Sciences University Of Fukui

• Uzui Hiroyasu

  京都大学 医学研究科循環器内科学

• Uzui Hiroyasu

  First Department Of Internal Medicine Fukui Medical University

• Ueda T

  First Department Of Internal Medicine Faculty Of Medical Sciences University Of Fukui

• Ueda Takanori

  福井大学医学部附属病院 循環器内科

• Ueda Takanori

  First Department Of Internal Medicine Faculty Of Medical Sciences University Of Fukui

• Uzui Hiroyasu

  First Department Of Internal Medicine Faculty Of Medical Sciences University Of Fukui

• Geshi Tohru

  Department Of Cardiovasucular Medicine Fukui University Hospital

• Toyoda Kiyohiro

  First Department of Internal medicine, Fukui University

• Lee Jong-dae

  Departments Of First Internal Medicine Fukui Medical University

• Geshi Tooru

  First Department of internal Medicine, Fukui Medical University

• Guo Hangyuan

  Department of Cardiology, Huayu Hospital, China Medical University

• Yue Hong

  First Department of Internal Medicine, Fukui Medical University

• Wang Junbo

  First Department of Internal Medicine, Fukui Medical University

• Toyoda Kiyohiro

  First Department Of Internal Medicine Fukui Medical University

• Yue Hong

  First Department Of Internal Medicine Fukui Medical University

• Wang Junbo

  First Department Of Internal Medicine Fukui Medical University

• Guo Hangyuan

  Department Of Cardiology Huayu Hospital China Medical University:first Department Of Internal Medici

• Lewis J

  Washington Univ. Medical Center St. Louis Usa

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