PKC-β is not necessary for cardiac hypertrophy
PKC-β is not necessary for cardiac hypertrophy
复制标题
DOI：
10.1152/ajpheart.2001.280.5.h2264
复制
发表时间：
2001-05-01
影响因子：
4.8
通讯作者：
Buttrick, PM
中科院分区：
文献类型：
--
作者：
Roman, BB;Geenen, DL;Buttrick, PM
在人类和啮齿动物模型中的研究表明，蛋白激酶C-β（PKC-β）的激活与病理性肥大的发生相关，这表明PKC-β通路的消融可能会预防或逆转心脏肥大。为了探索这一点，我们研究了PKC-β基因靶向破坏（敲除，KO）的小鼠。通过Western印迹分析，KO和对照心脏之间的其他PKC亚型的表达或分布没有可检测到的差异。使用闭胸准备测量基线血流动力学，心率和动脉或左心室压力无差异。对小鼠进行两种独立的肥大刺激：20 mg的苯丙氨酸（Phe）。kg（-1）。第（-1）天sq输注3天，主动脉结扎（AoB）7天。KO动物表现出心脏重量/体重比增加（Phe，4.3 +/- 0.6至6.1 +/- 0.4; AoB，4.0 +/- 0.1至5.8 +/- 0.7）以及心室心房利钠因子mRNA上调，与对照动物中观察到的相似。这些结果表明，PKC-β的表达是不必要的心脏肥大的发展，也没有削弱其缺乏肥大反应。
Studies in human and rodent models have shown that activation of protein kinase C-beta (PKC-beta) is associated with the development of pathological hypertrophy, suggesting that ablation of the PKC-beta pathway might prevent or reverse cardiac hypertrophy. To explore this, we studied mice with targeted disruption of the PKC-beta gene (knockout, KO). There were no detectable differences in expression or distribution of other PKC isoforms between the KO and control hearts as determined by Western blot analysis. Baseline hemodynamics were measured using a closed-chest preparation and there were no differences in heart rate and arterial or left ventricular pressure. Mice were subjected to two independent hypertrophic stimuli: phenylephrine (Phe) at 20 mg . kg(-1) . day(-1) sq infusion for 3 days, and aortic banding (AoB) for 7 days. KO animals demonstrated an increase in heart weight-to-body weight ratio (Phe, 4.3 +/- 0.6 to 6.1 +/- 0.4; AoB, 4.0 +/- 0.1 to 5.8 +/- 0.7) as well as ventricular upregulation of atrial natriuretic factor mRNA analogous to those seen in control animals. These results demonstrate that PKC-beta expression is not necessary for the development of cardiac hypertrophy nor does its absence attenuate the hypertrophic response.