Katoh Y, Komuro I, Yamaguchi H, Yazaki Y
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Jpn Circ J. 1992 Jul;56(7):694-700. doi: 10.1253/jcj.56.694.
The clinical syndrome of heart failure occurs as a consequence of the limitation of compensatory mechanisms, such as cardiac hypertrophy. To clarify transcriptional changes in specific genes in failing hearts, we examined the expression of cardiac Ca(2+)+Mg(2+)-dependent ATPase in the sarcoplasmic reticulum and transforming growth factor beta genes in the ventricles of rat hypertrophied heart, and the expression of guanine nucleotide-binding protein and "fetal" contractile protein genes in the ventricles of cardiomyopathic Syrian hamsters of Bio14.6. Northern blot analysis of total cellular RNA revealed that the mRNA levels of Ca(2+)+Mg(2+)-dependent ATPase were decreased by pressure overload and became 32% of sham in 1 month, and were correlated with corresponding protein levels. Transforming growth factor beta mRNA, a potent activator of collagen synthesis, was increased by pressure overload. The expression levels of the Gs alpha mRNA, which stimulated the adenylate cyclase, in Bio14.6 ventricles were lower than the levels in ventricles of the F1B hamster strain, and decreased as the stage of cardiomyopathy progressed. Moreover, re-expression of fetal mRNA was observed in the ventricle of cardiomyopathic Syrian hamsters of the Bio14.6 strain. These results indicate that reprogramming of cardiac gene expression both of myofibrillar and nonmyofibrillar components might occur in the failing heart.
心力衰竭的临床综合征是由于诸如心肌肥大等代偿机制受限而产生的。为了阐明衰竭心脏中特定基因的转录变化，我们检测了大鼠肥大心脏心室中肌浆网内的心脏钙（2 +）+镁（2 +）依赖性ATP酶以及转化生长因子β基因的表达，以及Bio14.6品系的心肌病叙利亚仓鼠心室中鸟嘌呤核苷酸结合蛋白和“胎儿型”收缩蛋白基因的表达。对总细胞RNA进行的Northern印迹分析显示，钙（2 +）+镁（2 +）依赖性ATP酶的mRNA水平因压力超负荷而降低，在1个月时降至假手术组的32%，且与相应的蛋白质水平相关。作为胶原合成强力激活剂的转化生长因子β mRNA因压力超负荷而增加。Bio14.6品系心室中刺激腺苷酸环化酶的Gsα mRNA表达水平低于F1B仓鼠品系心室中的水平，并随着心肌病的进展而降低。此外，在Bio14.6品系的心肌病叙利亚仓鼠心室中观察到胎儿型mRNA的重新表达。这些结果表明，在衰竭心脏中可能会发生肌原纤维和非肌原纤维成分的心脏基因表达重编程。
