FGF21 attenuates pathological myocardial remodeling following myocardial infarction through the adiponectin-dependent mechanism

被引：132

作者：

Joki, Yusuke ^{[1
,3
]}

Ohashi, Koji ^{[2
]}

Yuasa, Daisuke ^{[1
]}

Shibata, Rei ^{[1
]}

Ito, Masanori ^{[1
]}

Matsuo, Kazuhiro ^{[1
]}

Kambara, Takahiro ^{[1
]}

Uemura, Yusuke ^{[1
]}

Hayakawa, Satoko ^{[1
]}

Hiramatsu-Ito, Mizuho ^{[1
]}

Kanemura, Noriyoshi ^{[1
]}

Ogawa, Hayato ^{[1
]}

Daida, Hiroyuki ^{[3
]}

Murohara, Toyoaki ^{[1
]}

Ouchi, Noriyuki ^{[2
]}

机构：

[1] Nagoya Univ, Grad Sch Med, Dept Cardiol, Nagoya, Aichi 4668550, Japan

[2] Nagoya Univ, Grad Sch Med, Mol Cardiovasc Med, Nagoya, Aichi 4668550, Japan

[3] Juntendo Univ, Sch Med, Dept Cardiol, Tokyo 113, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2015年 / 459卷 / 01期

关键词：

FGF21; Myokine; Cardiac remodeling; Myocardial infarction; Adiponectin; FOLLISTATIN-LIKE; 1; GROWTH-FACTOR; 21; INSULIN-RESISTANCE; SKELETAL-MUSCLE; CROSS-TALK; MICE; PROTEIN; OBESITY; FIBROBLAST-GROWTH-FACTOR-21; METABOLISM;

D O I：

10.1016/j.bbrc.2015.02.081

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Ischemic heart disease is one of the leading causes of death. Fibroblast growth factor 21 (FGF21) is a circulating factor with an anti-diabetic property. Skeletal muscle is an important source of FGF21 production. Here, we investigated whether skeletal muscle-derived FGF21 modulates cardiac remodeling in a murine model of myocardial infarction. Myocardial infarction was produced in C57BL/6J wild-type (WT) mice by the permanent ligation of the left anterior descending coronary artery (LAD). Adenoviral vectors expressing FGF21 (Ad-FGF21) or control beta-galactosidase were intramuscularly injected into mice at 3 days before permanent LAD ligation. Intramuscular injection of Ad-FGF21 increased plasma FGF21 levels in WT mice compared with control. Treatment of WT mice with Ad-FGF21 led to improvement of left ventricular systolic dysfunction and dilatation at 2 weeks after LAD ligation. Ad-FGF21 administration to WT mice also led to enhancement of capillary density in the infarct border zone, and reduction of myocyte apoptosis in the remote zone, which were accompanied by decreased expression of pro-inflammatory cytokines. Furthermore, treatment of WT mice with Ad-FGF21 increased plasma levels of adiponectin, which is a cardioprotective adipokine. The beneficial effects of Ad-FGF21 on cardiac dysfunction and inflammatory response after myocardial infarction were diminished in adiponectin-knockout mice. These data suggest that muscle-derived FGF21 ameliorates adverse cardiac remodeling after myocardial infarction, at least in part, through an adiponectin-dependent mechanism. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：124 / 130

页数：7

共 33 条

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