Departamento de Genética e Evolução, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP Brazil.
Genet Mol Biol. 2010 Jan;33(1):12-6. doi: 10.1590/S1415-47572010005000004. Epub 2010 Mar 1.
Ventricular hypertrophy is one of the major myocardial responses to pressure overload (PO). Most studies on early myocardial response focus on the days or even weeks after induction of hypertrophic stimuli. Since mechanotransduction pathways are immediately activated in hearts undergoing increased work load, it is reasonable to infer that the myocardial gene program may be regulated in the first few hours. In the present study, we monitored the expression of some genes previously described in the context of myocardial hypertrophic growth by using the Northern blot technique, to estimate the mRNA content of selected genes in rat myocardium for the periods 1, 3, 6, 12 and 48 h after PO stimuli. Results revealed an immediate switch in the expression of genes encoding alpha and beta isoforms of myosin heavy chain, and up-regulation of the cardiac isoform of alpha actin. We also detected transitory gene regulation as the increase in mitochondrial cytochrome c oxidase 1 gene expression, parallel to down-regulation of genes encoding sarco(endo)plasmic reticulum Ca(+2) ATPase and sodium-calcium exchanger. Taken together, these results indicate that initial myocardial responses to increased work load include alterations in the contractile properties of sarcomeres and transitory adjustment of mitochondrial bioenergetics and calcium availability.
心室肥厚是心肌对压力超负荷(PO)的主要反应之一。大多数关于早期心肌反应的研究都集中在肥厚刺激后几天甚至几周。由于机械转导途径在心脏负荷增加时立即被激活,因此可以合理地推断心肌基因程序可能在最初的几个小时内受到调节。在本研究中,我们使用 Northern blot 技术监测了一些先前在心肌肥厚生长背景下描述的基因的表达,以估计大鼠心肌在 PO 刺激后 1、3、6、12 和 48 小时内选定基因的 mRNA 含量。结果显示,肌球蛋白重链的α和β同工型编码基因的表达立即发生转换,α肌动蛋白的心脏同工型上调。我们还检测到基因表达的瞬时调节,即线粒体细胞色素 c 氧化酶 1 基因表达增加,同时肌浆网(内)钙 ATP 酶和钠钙交换体编码基因下调。总之,这些结果表明,心肌对增加工作量的初始反应包括肌节收缩特性的改变以及线粒体生物能量和钙可用性的短暂调整。