MYOSIN ISOENZYMES IN MYOCARDIAL HYPERTROPHY

心肌肥厚中的肌球蛋白同工酶

• 批准号: 3448553
• 负责人: GREGORY D CURFMAN
• 金额: $ 4.84万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-01-01 至 1985-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3448553
• 关键词: adenosinetriphosphatase; congestive heart failure; heart contraction; hemodynamics; human tissue; isozymes; molecular pathology; ventricular hypertrophy

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.

心脏肥大是心脏对血液动力学的基本适应 超负荷，并往往伴随着心肌的变化， 收缩性 变化的方向和幅度取决于 肥大刺激的类型、持续时间和严重程度。 相当大 有证据表明，这些收缩功能的慢性变化可能是 部分由肌球蛋白腺苷活性的改变介导 三磷酸酶（ATP酶）。 这种酶为肌肉提供能量 收缩，其活动与最大速度密切相关 肌肉缩短。 本研究的具体目的是 研究肌球蛋白ATP酶变化的分子机制， 活动发生在心脏肥大的发展过程中。 可用 在大鼠和兔子中的证据表明，肌球蛋白可能至少以 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ATP酶活性。 三者的相对命题 同工酶可以决定肌球蛋白库的总ATP酶活性。 的 工作假设是对心脏肥大的不同刺激（例如， 压力超负荷和甲状腺激素）可能会促进 不同的肌球蛋白同工酶取决于功能要求 放置在心肌上。 这一假设将被直接测试 测量心肌肌球蛋白的合成、降解和半衰期的速率 同工酶 这些测量将在正常大鼠中进行， 甲状腺切除动物、甲状腺功能亢进动物和 主动脉瓣致左心室压力超负荷动物 带状。 通过这种方式，不同的肥大刺激对 肌球蛋白同工酶周转和由此产生的同工酶分布 将研究心肌内的情况。 这些实验旨在 为进一步了解肌球蛋白同工酶在心肌梗死中的作用， 心脏适应不同的血液动力学条件，并可能承担 充血性心力衰竭这一重要的临床问题。 未来 研究的目的是确定人类肌球蛋白同工酶的模式， 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。