ACIDIC FIBROBLAST GROWTH-FACTOR AND HEART DEVELOPMENT - ROLE IN MYOCYTE PROLIFERATION AND CAPILLARY ANGIOGENESIS
ACIDIC FIBROBLAST GROWTH-FACTOR AND HEART DEVELOPMENT - ROLE IN MYOCYTE PROLIFERATION AND CAPILLARY ANGIOGENESIS
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DOI：
10.1161/01.res.72.1.7
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发表时间：
1993-01-01
影响因子：
20.1
通讯作者：
JAYE, MC
中科院分区：
文献类型：
--
作者：
ENGELMANN, GL;DIONNE, CA;JAYE, MC
心室肌细胞（心肌细胞）的增殖性生长主要限于胎儿和早期新生儿发育期。与新生儿从增殖性到肥大性生长的“过渡”一致，非肌细胞室的心室重塑的特征在于细胞外基质合成/沉积增加和毛细血管新生。局部产生的和生物活性的心室酸性成纤维细胞生长因子（aFGF）在这些过程中的作用提出并通过以下内容得到证实：1）通过免疫组织化学、免疫电子显微镜和原位杂交将aFGF肽和成纤维细胞生长因子受体（FGF）转录物共定位于发育中的胎儿心肌细胞，2）将aFGF肽和转录物持续定位于新生/成熟心肌细胞，和3）定位的ESTA免疫反应和转录到特定的新生儿心室非肌细胞类型。不同发育阶段的特定心室细胞类型似乎对心室肌细胞衍生的aFGF（胎儿心脏中的肌细胞和新生儿心脏中的非肌细胞/内皮细胞）有反应。这些数据表明，aFGF及其受体之一（bFGF）的表达在胎儿至早期新生儿心室中最明显，两者的存在表明自分泌/旁分泌生长调节功能。随着动物的成熟，心室毛细血管生成可以通过心肌细胞衍生的成纤维细胞生长因子“释放"到周围的细胞外空间/基质中作为”旁分泌"血管生成刺激来促进。因此，我们的研究结果表明，肌细胞衍生的aFGF可能起到增加胎儿心室心肌细胞绝对数量的作用，以及促进随后在心肌细胞成熟和心室重塑过程中发生的毛细血管新生的增加。
Proliferative growth of the ventricular myocyte (cardiomyocyte) is primarily limited to fetal and early neonatal periods of development. In concert with the neonatal ''transition'' from proliferative to hypertrophic growth, ventricular remodeling of the nonmyocyte compartment is characterized by increased extracellular matrix synthesis/deposition and capillary angiogenesis. A role for locally generated and bioactive ventricular acidic fibroblast growth factor (aFGF) in these processes is proposed and substantiated by the following: 1) colocalization of aFGF peptide and fibroblast growth factor receptor (flg) transcripts to the developing fetal cardiomyocyte by immunohistochemistry, immunoelectron microscopy, and in situ hybridization, 2) continued localization of aFGF peptide and transcripts to the neonatal/mature cardiomyocyte, and 3) localization of flg immunoreactivity and transcripts to specific neonatal ventricular nonmuscle cell types. Specific ventricular cell types at distinct developmental stages appear to be responsive to ventricular myocyte-derived aFGF (myocytes in the fetal heart and nonmyocytes/endothelial cells in the neonatal heart). These data indicate that expression of aFGF and one of its receptors (flg) are most pronounced in the fetal to early neonatal ventricle, the presence of both suggesting an autocrine/paracrine growth regulatory function. As the animal matures, ventricular capillary angiogenesis may be facilitated by ''release'' of cardiomyocyte-derived fibroblast growth factors into the surrounding extracellular space/matrix functioning as a ''paracrine'' angiogenic stimuli. Therefore, the results of our study suggest that myocyte-derived aFGF may function to increase the fetal ventricular cardiomyocyte population in absolute number as well as to facilitate the subsequent increase in capillary angiogenesis that occurs during cardiomyocyte maturation and ventricular remodeling.