THE VASCULAR SMOOTH-MUSCLE ALPHA-ACTIN GENE IS REACTIVATED DURING CARDIAC-HYPERTROPHY PROVOKED BY LOAD
THE VASCULAR SMOOTH-MUSCLE ALPHA-ACTIN GENE IS REACTIVATED DURING CARDIAC-HYPERTROPHY PROVOKED BY LOAD
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DOI：
10.1172/jci115470
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发表时间：
1991-11-01
影响因子：
15.9
通讯作者：
SCHNEIDER, MD
中科院分区：
文献类型：
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作者：
BLACK, FM;PACKER, SE;SCHNEIDER, MD
机械负荷引起的心肌肥厚具有生长因子信号转导的共同特征。血流动力学负荷会刺激生长因子诱导的核癌基因c-fos的快速表达，某些肽生长因子甚至在没有负荷的情况下也会特异性地刺激与肥厚相关的“胎儿”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，这是在心肌发生过程中表达的最早的α-肌动蛋白；然而，尚不清楚在心肌肥厚中是否发生了平滑肌α-肌动蛋白基因的重新激活。因此，我们研究了血流动力学超负荷后心肌中α-肌动蛋白基因的表达。在肥厚心脏中，平滑肌α-肌动蛋白基因诱导率为0.909，而骨骼肌α-肌动蛋白基因诱导率为0.545(P<0.05)。与骨骼肌α-肌动蛋白相关系数差异有统计学意义(r=0.852；P=0.0001)，而与骨骼肌α-肌动蛋白基因活性相关性较差(r=0.532；P=0.009)。因此，平滑肌α-肌动蛋白是压力超负荷肥厚的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-肌动蛋白相同。主动脉缩窄后，平滑肌α-肌动蛋白的诱导延迟并持续，而核癌基因c-jun和JunB迅速和短暂地表达，为c-fos转录调控提供了潜在的二聚体伙伴。
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 < 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 < 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.