High- but not low-molecular weight FGF-2 causes cardiac hypertrophy in vivo;: possible involvement of cardiotrophin-1
High- but not low-molecular weight FGF-2 causes cardiac hypertrophy in vivo;: possible involvement of cardiotrophin-1
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DOI：
10.1016/j.yjmcc.2006.09.002
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发表时间：
2007-01-01
影响因子：
5
通讯作者：
Kardami, Elissavet
中科院分区：
文献类型：
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作者：
Jiang, Zhi-Sheng;Jeyaraman, Madhumathy;Kardami, Elissavet
心脏表达高分子量和低分子量（hmw、lmw）成纤维细胞生长因子2（FGF-2）同种型。虽然lmw-FGF-2的损伤修复相关活性已被广泛研究，但hmw-FGF-2的损伤修复相关活性尚未被广泛研究。因此，我们研究了hmw-FGF-2对大鼠不可逆冠状动脉闭塞诱导的心肌梗死（MI）的急性和慢性反应的影响。Hmw-或lmw-FGF-2在急性进展性MI期间被注射到缺血区中。两种亚型在减少梗死面积（在MI后24小时）和改善心脏功能至MI后6周方面与溶剂处理的梗死组相比同样有效。Lmw-FGF-2单独上调梗死中的血管形成。Hmw-FGF-2引起显着的肥大，相比。在MI后4-8周，通过超声、心脏形态测量和心肌细胞横截面积评估赋形剂治疗组。此外，hmw-（但不是lmw-）FGF-2处理的心脏显示细胞因子心肌营养素-1及其信号转导蛋白gp 130的积累增加。在培养中，hmw-（而不是lmw-）FGF-2增加心肌细胞蛋白质合成和细胞大小，以及上调心脏成纤维细胞释放的心肌营养素-I，在体内具有类似的活性。因此，hmw-和lmwFGF-2在心脏中发挥同种型特异性作用，并且只有hmw-FGF-2触发心肌细胞肥大生长。hmw-FGF-2对心肌细胞的直接作用，通过心肌营养素-I的上调并与其他因素协同作用而得到加强和维持，可能有助于MI后肥大。(c)2006年爱思唯尔公司All rights reserved.
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.