Cytoskeletal networks and the regulation of cardiac contractility: microtubules, hypertrophy, and cardiac dysfunction
Cytoskeletal networks and the regulation of cardiac contractility: microtubules, hypertrophy, and cardiac dysfunction
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DOI：
10.1152/ajpheart.00132.2006
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发表时间：
2006-09-01
影响因子：
4.8
通讯作者：
Cooper, George
中科院分区：
文献类型：
--
作者：
Cooper, George
经典定义的真核细胞的细胞骨架由三个蛋白质丝系统组成：微管、中间丝和微丝。在成熟的横纹肌中，例如成年哺乳动物的心脏，这三种类型的细胞骨架丝在空间上叠加在肌丝上，肌丝是一种特殊的收缩蛋白丝系统。这些蛋白质丝系统中的每一个都有可能在负荷诱导的肥厚心脏生长过程中以适应性或适应不良的方式做出反应。然而，这种肥大的代偿程度也很大程度上取决于作为肥大刺激的血流动力学超负荷的类型。因此，心脏肥大本质上并不是适应不良。相反，正是诱导负荷的性质而不是肥大本身，通过对结构和/或调节蛋白的影响，导致最初代偿性肥大经常恶化为充血性心力衰竭状态。作为这里回顾的这种适应不良的负荷特异性的一个例子，增加的微管网络密度是严重压力超负荷、肥大和衰竭的心肌的一个持续特征，它在收缩期间对活跃的肌丝施加主要的粘性负荷。
The cytoskeleton as classically defined for eukaryotic cells consists of three systems of protein filaments: the microtubules, the intermediate filaments, and the microfilaments. In mature striated muscle such as the heart of the adult mammal, these three types of cytoskeletal filaments are superimposed spatially on the myofilaments, a specialized system of contractile protein filaments. Each of these systems of protein filaments has the potential to respond in an adaptive or maladaptive manner during load-induced hypertrophic cardiac growth. However, the extent to which such hypertrophy is compensatory is also critically dependent on the type of hemodynamic overload that serves as the hypertrophic stimulus. Thus cardiac hypertrophy is not intrinsically maladaptive; rather, it is the nature of the inducing load rather than hypertrophy itself that is responsible, through effects on structural and/or regulatory proteins, for the frequent deterioration of initially compensatory hypertrophy into the congestive heart failure state. As one example reviewed here of this load specificity of maladaptation, increased microtubule network density is a persistent feature of severely pressure-overloaded, hypertrophied, and failing myocardium that imposes a primarily viscous load on active myofilaments during contraction.