High-mobility group box 1 restores cardiac function after myocardial infarction in transgenic mice

被引：150

作者：

Kitahara, Tatsuro ^{[2
]}

Takeishi, Yasuchika ^{[1
]}

Harada, Mutsuo ^{[2
]}

Niizeki, Takeshi ^{[2
]}

Suzuki, Satoshi ^{[2
]}

Sasaki, Toshiki ^{[2
]}

Ishino, Mitsunori ^{[2
]}

Bilim, Olga ^{[2
]}

Nakajima, Osamu ^{[3
]}

Kubota, Isao ^{[2
]}

机构：

[1] Fukushima Med Univ, Dept Internal Med 1, Fukushima 9601295, Japan

[2] Yamagata Univ, Sch Med, Dept Cardiol Pulmonol & Nephrol, Yamagata 99023, Japan

[3] Yamagata Univ, Sch Med, Mol Genet Res Lab, Yamagata 99023, Japan

来源：

CARDIOVASCULAR RESEARCH | 2008年 / 80卷 / 01期

关键词：

HMGB1; cardiac remodelling; myocardial infarction; angiogenesis;

D O I：

10.1093/cvr/cvn163

中图分类号：

R5 [内科学];

学科分类号：

1002 [临床医学]; 100201 [内科学];

摘要：

Aims High-mobility group box 1 (HMGB1) is a nuclear DNA-binding protein and is released from necrotic cells, inducing inflammatory responses and promoting tissue repair and angiogenesis. To test the hypothesis that HMGB1 enhances angiogenesis and restores cardiac function after myocardial infarction (MI), we generated transgenic mice with cardiac-specific overexpression of HMGB1 (HMGB1-Tg) using alpha-myosin heavy chain promoter. Methods and results The left anterior descending coronary artery was ligated in HMGB1-Tg and wild-type littermate (Wt) mice. After coronary artery ligation, HMGB1 was released into circulation from the necrotic cardiomyocytes of HMGB1-overexpressing hearts. The size of MI was smaller in HMGB1-Tg than in Wt mice. Echocardiography and cardiac catheterization demonstrated that cardiac remodelling and dysfunction after MI were prevented in HMGB1-Tg mice compared with Wt mice. Furthermore, the survival rate after MI of HMGB1-Tg mice was higher than that of Wt mice. Immunohistochemical staining revealed that capillary and arteriole formation after MI was enhanced in HMGB1-Tg mice. Conclusion We report the first in vivo evidence that HMGB1 enhances angiogenesis, restores cardiac function, and improves survival after MI. These results may provide a novel therapeutic approach for left ventricular dysfunction after MI.

引用

页码：40 / 46

页数：7

共 31 条

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