Black F M, Packer S E, Parker T G, Michael L H, Roberts R, Schwartz R J, Schneider M D
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
J Clin Invest. 1991 Nov;88(5):1581-8. doi: 10.1172/JCI115470.
Cardiac hypertrophy triggered by mechanical load possesses features in common with growth factor signal transduction. A hemodynamic load provokes rapid expression of the growth factor-inducible nuclear oncogene, c-fos, and certain peptide growth factors specifically stimulate the "fetal" cardiac genes associated with hypertrophy, even in the absence of load. These include the gene encoding vascular smooth muscle alpha-actin, the earliest alpha-actin expressed during cardiac myogenesis; however, it is not known whether reactivation of the smooth muscle alpha-actin gene occurs in ventricular hypertrophy. We therefore investigated myocardial expression of the smooth muscle alpha-actin gene after hemodynamic overload. Smooth muscle alpha-actin mRNA was discernible 24 h after coarctation and was persistently expressed for up to 30 d. In hypertrophied hearts, the prevalence of smooth muscle alpha-actin gene induction was 0.909, versus 0.545 for skeletal muscle alpha-actin (P less than 0.05). Ventricular mass after 2 d or more of aortic constriction was more highly correlated with smooth muscle alpha-actin gene activation (r = 0.852; P = 0.0001) than with skeletal muscle alpha-actin (r = 0.532; P = 0.009); P less than 0.0005 for the difference in the correlation coefficients. Thus, smooth muscle alpha-actin is a molecular marker of the presence and extent of pressure-overload hypertrophy, whose correlation with cardiac growth at least equals that of skeletal alpha-actin. Induction of smooth muscle alpha-actin was delayed and sustained after aortic constriction, whereas the nuclear oncogenes c-jun and junB were expressed rapidly and transiently, providing potential dimerization partners for transcriptional control by c-fos.
机械负荷引发的心脏肥大具有与生长因子信号转导相同的特征。血流动力学负荷可促使生长因子诱导型核癌基因c-fos快速表达，某些肽生长因子即使在无负荷情况下也能特异性刺激与肥大相关的“胎儿型”心脏基因。这些基因包括编码血管平滑肌α-肌动蛋白的基因，它是心肌发生过程中最早表达的α-肌动蛋白；然而，尚不清楚平滑肌α-肌动蛋白基因的重新激活是否发生在心室肥大中。因此，我们研究了血流动力学过载后平滑肌α-肌动蛋白基因的心肌表达情况。缩窄术后24小时可检测到平滑肌α-肌动蛋白mRNA，并持续表达长达30天。在肥大心脏中，平滑肌α-肌动蛋白基因诱导的发生率为0.909，而骨骼肌α-肌动蛋白为0.545（P<0.05）。主动脉缩窄2天或更长时间后的心室质量与平滑肌α-肌动蛋白基因激活的相关性更高（r = 0.852；P = 0.0001），而与骨骼肌α-肌动蛋白的相关性较低（r = 0.532；P = 0.009）；相关系数差异的P<0.0005。因此，平滑肌α-肌动蛋白是压力超负荷肥大存在和程度的分子标志物，其与心脏生长的相关性至少与骨骼肌α-肌动蛋白相当。主动脉缩窄后平滑肌α-肌动蛋白的诱导延迟且持续，而核癌基因c-jun和junB快速且短暂表达，为c-fos的转录控制提供了潜在的二聚体伙伴。
