Roman B B, Geenen D L, Leitges M, Buttrick P M
Section of Cardiology, Department of Medicine, University of Illinois at Chicago, Illinois 60612, USA.
Am J Physiol Heart Circ Physiol. 2001 May;280(5):H2264-70. doi: 10.1152/ajpheart.2001.280.5.H2264.
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 x kg(-1) x 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.
对人类和啮齿动物模型的研究表明，蛋白激酶C-β（PKC-β）的激活与病理性肥大的发展相关，这表明消除PKC-β信号通路可能预防或逆转心脏肥大。为了探究这一点，我们研究了PKC-β基因靶向敲除的小鼠（基因敲除小鼠，KO）。通过蛋白质印迹分析确定，KO小鼠和对照小鼠心脏中其他PKC同工型的表达或分布没有可检测到的差异。使用闭胸制备法测量基线血流动力学，心率、动脉压或左心室压力没有差异。小鼠接受两种独立的肥大刺激：以20 mg·kg⁻¹·d⁻¹的剂量皮下注射去氧肾上腺素（Phe）3天，以及进行主动脉缩窄（AoB）7天。KO小鼠的心脏重量与体重比增加（Phe刺激组，从4.3±0.6增加到6.1±0.4；AoB刺激组，从4.0±0.1增加到5.8±0.7），并且心室中的心钠素mRNA上调，这与对照动物的情况类似。这些结果表明，PKC-β的表达对于心脏肥大的发展不是必需的，其缺失也不会减弱肥大反应。
