Parker T G
Toronto Hospital, Department of Medicine, University of Toronto, Ontario, Canada.
Herz. 1993 Aug;18(4):245-55.
Pressure-overload cardiac hypertrophy involves not only cellular growth but also reexpression of an extensive "fetal" program of cardiac-specific genes, providing an intriguing system in which to explore molecular signals which transduce altered load. Fibroblast and transforming growth factors are representative of trophic polypeptides produced by myocardium, which are regulated during cardiac morphogenesis and induced by myocardial ischemia, infarction, and load. Growth factors provoke a pattern of gene expression in cultured cardiac myocytes resembling pressure overload in vivo, implying a possible autocrine or paracrine model of cardiac hypertrophy. Growth-factor inducible cellular oncogenes are also expressed in myocardium, upregulated by hemodynamic load, and encode proteins which modulate the cardiac phenotype, in keeping with a possible functional role in growth factor and load-induced intracellular signalling. Demonstration of physiologic implications of growth factor and cellular oncogene expression in the heart awaits application of new technologies in molecular genetics and could herald novel therapeutic interventions for myocardial disease.
压力超负荷性心肌肥大不仅涉及细胞生长，还涉及广泛的心脏特异性基因“胎儿”程序的重新表达，这为探索转导负荷改变的分子信号提供了一个有趣的系统。成纤维细胞生长因子和转化生长因子是心肌产生的营养多肽的代表，它们在心脏形态发生过程中受到调节，并由心肌缺血、梗死和负荷诱导产生。生长因子在培养的心肌细胞中引发一种基因表达模式，类似于体内压力超负荷，这意味着心肌肥大可能存在自分泌或旁分泌模型。生长因子诱导的细胞癌基因也在心肌中表达，受血流动力学负荷上调，并编码调节心脏表型的蛋白质，这与它们在生长因子和负荷诱导的细胞内信号传导中可能发挥的功能作用一致。生长因子和细胞癌基因在心脏中表达的生理学意义的证明有待分子遗传学新技术的应用，并且可能预示着对心肌疾病的新型治疗干预措施。
