Mechanisms of cardiac hypertrophy in canine volume overload.
Mechanisms of cardiac hypertrophy in canine volume overload.
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DOI：
10.1152/ajpheart.1998.275.1.h65
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发表时间：
1998-07
期刊：
影响因子：
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通讯作者：
T. Matsuo;B. Carabello;Y. Nagatomo;M. Koide;M. Hamawaki;M. Zile;P. McDermott
中科院分区：
文献类型：
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作者：
T. Matsuo;B. Carabello;Y. Nagatomo;M. Koide;M. Hamawaki;M. Zile;P. McDermott
本研究测试了犬中因二尖瓣返流而发生的中度肥大是否是由于蛋白质合成速率相对较小的变化，或者是由于蛋白质降解速率降低。重度实验性二尖瓣返流3个月后，左心室（LV）质量-体重比与基线值相比增加了23%。左心室质量的增加伴随肌球蛋白重链（MHC）合成（Ks）分数的小幅增加，但无统计学显著性，这是在犬中建立重度二尖瓣返流后2周、4周和3个月使用[3 H]亮氨酸持续输注测量的。翻译效率是不受二尖瓣返流的多核糖体梯度中的MHC mRNA的分布测量。此外，通过总RNA含量或核糖体形成速率测量，翻译能力没有可检测到的增加。这些数据表明，加速心脏蛋白质合成速率的翻译机制对二尖瓣返流的刺激没有反应。二尖瓣返流后的大部分生长是由蛋白质降解率降低引起的，通过从相应的Ks值中减去每个时间点的蛋白质蓄积率来计算。我们得出结论：1）重度二尖瓣返流产生的容量超负荷不会引发蛋白质合成速率的显著增加，2）LV质量的适度增加主要是由于蛋白质降解速率的降低。
This study tested whether the modest hypertrophy that develops in dogs in response to mitral regurgitation is due to a relatively small change in the rate of protein synthesis or, alternatively, is due to a decreased rate of protein degradation. After 3 mo of severe experimental mitral regurgitation, the left ventricular (LV) mass-to-body weight ratio increased by 23% compared with baseline values. This increase in LV mass occurred with a small, but not statistically significant, increase in the fractional rate of myosin heavy chain (MHC) synthesis (Ks), as measured using continuous infusion with [3H]leucine in dogs at 2 wk, 4 wk, and 3 mo after creation of severe mitral regurgitation. Translational efficiency was unaffected by mitral regurgitation as measured by the distribution of MHC mRNA in polysome gradients. Furthermore, there was no detectable increase in translational capacity as measured by either total RNA content or the rate of ribosome formation. These data indicate that translational mechanisms that accelerate the rate of cardiac protein synthesis are not responsive to the stimulus of mitral regurgitation. Most of the growth after mitral regurgitation was accounted for by a decrease in the fractional rate of protein degradation, calculated by subtracting fractional rates of protein accumulation at each time point from the corresponding Ks values. We conclude that 1) volume overload produced by severe mitral regurgitation does not trigger substantial increases in the rate of protein synthesis and 2) the modest increase in LV mass results primarily from a decrease in the rate of protein degradation.