MYOSIN ISOENZYMES IN MYOCARDIAL HYPERTROPHY

心肌肥厚是心脏对血流动力学的一种基本适应 超负荷，常伴有心肌细胞的改变 伸缩性。变化的方向和大小由 肥大刺激的类型、持续时间和严重程度。相当可观 有证据表明，这些慢性收缩功能的变化可能是 肌球蛋白腺苷活性的改变在一定程度上调节了肌球蛋白的活性 三磷酸酶(ATPase)。这种酶为肌肉提供能量。 收缩，其活动与最大运动速度密切相关 肌肉变短。这项研究的具体目的是 肌球蛋白ATPase变化的分子机制研究(S) 活动发生在心肌肥厚的发展过程中。可用 在老鼠和兔子身上的证据表明，肌球蛋白可能至少作为 在这些物种中有三种不同的同工酶，每一种都有 其自身固有的ATPase活性。三者的相对提法 同工酶可以决定肌球蛋白池的总ATPase活性。这个 工作假说是不同的刺激对心肌肥厚(例如， 压力超负荷和甲状腺激素)可能促进合成 根据功能要求不同的肌球蛋白同工酶 放置在心肌上。这一假说将直接通过 测定心肌肌球蛋白的合成、降解和半衰期 同工酶。这些测量将在正常大鼠身上进行，并与 在甲状腺切除动物、甲亢动物和 主动脉致左室压超负荷的动物模型 班丁。在这种情况下，不同的肥大刺激对心肌细胞的影响 肌球蛋白同工酶周转及其同工酶的分布 将在心肌内进行研究。这些实验的目的是 以提供有关肌球蛋白同工酶在 心脏对不同血流动力学条件的适应，并可能承受 关于充血性心力衰竭这一重要的临床问题。未来 这项研究的目的是确定人类的肌球蛋白同工酶类型 心脏，并研究人类心脏疾病的影响 心肌病对肌球蛋白同工酶分布的影响。

Cardiac hypertrophy is a fundamental adaptation of the heart to hemodynamic overload, and it is often accompanied by changes in myocardial contractility. The direction and magnitude of change are determined by the type, duration, and severity of the stimulus to hypertrophy. Considerable evidence suggest that these chronic changes in contractile function may be mediated in part by alterations in the activity of myosin adenosine triphosphatase (ATPase). This enzyme provides energy for muscle contraction, and its activity correlates closely with the maximal velocity of muscle shortening. It is the specific purpose of this research to investigate the molecular mechanism(s) by which changes in myosin ATPase activity occur during the development of cardiac hypertrophy. Available evidence in the rat and rabbit suggests that myosin may exist as at least three electrophoretically distinct isoenzymes in these species, each with its own intrinsic ATPase activity. The relative propostions of the three isoenzymes may determine the total ATPase activity of the myosin pool. The working hypothesis is that different stimuli to cardiac hypertrophy (e.g., pressure overload and thyroid hormone) may promote the synthesis of different myosin isoenzymes depending upon the functional requirements placed upon the myocardium. This hypothesis will be tested by directly measuring rates of synthesis, degradation, and half-lives of cardiac myosin isoenzymes. These measurements will be made in normal rats, and compared to values obtained in thyroidectomized animals, hyperthyroid animals, and animals with left ventricular pressure overload produced by aortic banding. In this way the effects of different hypertrophic stimuli on myosin isoenzyme turnover and the resulting distribution of isoenzymes within the myocardium will be investigated. These experiments are intended to provide further information about the role of myosin isoenzymes in the adaptation of the heart to different hemodynamic conditions, and may bear upon the important clinical problem of congestive heart failure. Future research will be aimed at defining myosin isoenzyme patterns in the human heart, and studying the effect of human cardiac diseases such as cardiomyopathies on myosin isoenzyme distribution.