Overexpression of tumor necrosis factor-α increases production of hydroxyl radical in murine myocardium

被引:37
作者
Machida, Y [1 ]
Kubota, T [1 ]
Kawamura, N [1 ]
Funakoshi, H [1 ]
Ide, T [1 ]
Utsumi, H [1 ]
Li, YY [1 ]
Feldman, AM [1 ]
Tsutsui, H [1 ]
Shimokawa, H [1 ]
Takeshita, A [1 ]
机构
[1] Kyushu Univ, Dept Cardiovasc Med, Grad Sch Med, Higashi Ku, Fukuoka 8128582, Japan
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2003年 / 284卷 / 02期
关键词
cytokine; heart failure; reactive oxygen species;
D O I
10.1152/ajpheart.00581.2002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Transgenic (TG) mice with cardiac-specific overexpression of tumor necrosis factor-alpha develop congestive heart failure with myocardial inflammation. The purpose of this study was to investigate the effects of tumor necrosis factor-alpha on reactive oxygen species (ROS) in this mouse model of cardiomyopathy. Myocardial production of hydroxyl radical detected by electron spin resonance spectroscopy was significantly increased in TG. Myocardial expression of Mn-SOD was significantly decreased in TG, whereas that of Cu,Zn-SOD was unaltered. Myocardial expression of catalase was unchanged, whereas that of glutathione peroxidase was significantly increased, in TG. Histological analysis revealed that macrophages and CD4-positive lymphocytes were increased in TG myocardium. To investigate whether these infiltrating inflammatory cells were the source of ROS, we treated TG mice with cyclophosphamide for 7 days. Although cyclophosphamide significantly suppressed the infiltration of inflammatory cells, it did not diminish the production of hydroxyl radical in TG myocardium. Damaged myocytes, but not infiltrating inflammatory cells, may be the source of ROS in TG.
引用
收藏
页码:H449 / H455
页数:7
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