Transgenic myocardial overexpression of fibroblast growth factor-1 increases coronary artery density and branching
Transgenic myocardial overexpression of fibroblast growth factor-1 increases coronary artery density and branching
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DOI：
10.1161/01.res.87.3.207
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发表时间：
2000-08-04
影响因子：
20.1
通讯作者：
Zimmermann, R
中科院分区：
文献类型：
--
作者：
Fernandez, B;Buehler, A;Zimmermann, R
成纤维细胞生长因子（FGF）-1在心肌和冠状动脉形态发生过程中起重要作用。FGF - 1也参与成年心脏对缺血的生理反应，包括心肌细胞保护和血管生长。在本研究中，我们培育了基因在心肌特异性过表达的转基因小鼠。通过Northern杂交验证了转基因的表达，通过Western杂交和免疫共聚焦显微镜检测到FGF - 1蛋白含量增加。解剖学、组织形态学和超微结构分析显示转基因心脏没有重大的形态或发育异常。毛细血管密度未改变，而冠状动脉（尤其是小动脉）的密度显著增加，冠状动脉主干的分支数量也增加。此外，在体外实验中，转基因小鼠的冠状动脉血流显著增强。冠状动脉血管系统的这些解剖结构差异在出生后第二个月形成。本研究结果表明FGF - 1在冠状动脉系统的分化和生长中起重要作用，并提示它是动脉系统分化的关键调节分子。
Fibroblast growth factor (FGF)-1 plays important roles during myocardial and coronary morphogenesis. FGF-1 is also involved in the physiological response of the adult heart against ischemia, which includes cardiomyocyte protection and vascular growth. In the present study, we have generated transgenic mice with specific myocardial overexpression of the gene. Transgene expression was verified by Northern blot, and increased FGF-1 protein content was assessed by Western blot and immunoconfocal microscopy. Anatomic, histomorphological, and ultrastructural analyses revealed no major morphological or developmental abnormalities of transgenic hearts. Capillary density was unaltered, whereas the density of coronary arteries, especially arterioles, was significantly increased, as was the number of branches of the main coronary arteries. In addition, the coronary flow was significantly enhanced in transgenic mice ex vivo. These differences in the anatomic pattern of the coronary vasculature are established during the second month of postnatal life. The present findings demonstrate an important role of FGF-1 in the differentiation and growth of the coronary system and suggest that it is a key regulatory molecule of the differentiation of the arterial system.