High- but not low-molecular weight FGF-2 causes cardiac hypertrophy in vivo;: possible involvement of cardiotrophin-1

被引:59
作者
Jiang, Zhi-Sheng
Jeyaraman, Madhumathy
Wen, Ge-Bo
Fandrich, Robert R.
Dixon, Ian M. C.
Cattini, Peter A.
Kardami, Elissavet [1 ]
机构
[1] Univ Manitoba, St Boniface Res Ctr, Inst Cardiovasc Sci, Winnipeg, MB R2H 2A6, Canada
[2] Univ Manitoba, Dept Human Anat, Winnipeg, MB R2H 2A6, Canada
[3] Univ Manitoba, Dept Cell Sci, Winnipeg, MB R2H 2A6, Canada
[4] Univ Manitoba, Dept Physiol, Winnipeg, MB R2H 2A6, Canada
基金
中国国家自然科学基金; 加拿大健康研究院;
关键词
FGF-2; isoforms; cardiac hypertrophy; cardiotrophin-1; cardioprotection;
D O I
10.1016/j.yjmcc.2006.09.002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The heart expresses high and low molecular weight (hmw, lmw) fibroblast growth factor 2 (FGF-2) isoforms. While the injury-repair-related activities of lmw-FGF-2 have been studied extensively, those of hmw-FGF-2 have not. Thus, we investigated the effects of hmw-FGF-2 on acute as well as chronic responses to myocardial infarction (MI) induced by irreversible coronary occlusion in the rat. Hmw- or lmw-FGF-2 was injected into the ischemic zone during acute evolving MI. Both isoforms were equally effective in reducing infarct size (at 24 h post-MI) and improving heart function up to 6 weeks post-MI, compared to a vehicle-treated infarcted group. Lmw-FGF-2 alone upregulated vascularization in the infarct. Hmw-FGF-2 elicited significant hypertrophy, compared to the. vehicle-treated group, at 4-8 weeks post-MI, assessed by ultrasound, heart morphometry and cardiomyocyte cross-sectional area. In addition, hmw- (but not lmw-) FGF-2-treated hearts displayed increased accumulation of the cytokine cardiotrophin-l and its signal transducer gp130. In culture, hmw- (but not lmw-) FGF-2 increased cardiomyocyte protein synthesis and cell size as well as upregulated cardiotrophin-I released by cardiac fibroblasts, pointing to similar activities in vivo. Thus, hmw- and lmwFGF-2 exert isoform-specific effects in the heart and only hmw-FGF-2 triggers cardiomyocyte hypertrophic growth. Direct effects of hmw-FGF-2 on cardiomyocytes, becoming reinforced and sustained by upregulation of cardiotrophin-I and acting in concert with other factors, are likely to contribute to post-MI hypertrophy. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:222 / 233
页数:12
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