CELLULAR MECHANISMS IN CARDIAC HYPERTROPY

这项提案是对细胞和 生物力学性能改变的生物化学基础 心脏肥大和衰竭。大鼠和兔心肌梗死后心脏 将对失效模式进行研究。重点放在甲状腺激素上 (T3)诱导的肥厚，因为机械性能增强，以及 对这种肥大形式的洞察可能会提供一种理性的 为开发T3类似物作为变力药物奠定了基础。在这 续签申请，请求支持五个项目：1) 肌球蛋白重链表达调控的分子基础 包括调控蛋白的克隆和鉴定。 2)自主神经系统在心脏调节中的作用 增长和业绩。3)顺畅收缩的调节 肌肉，特别是关于磷酸酶在控制中的作用 肌球蛋白的磷酸化。4)一个新的项目将是 开始研究心脏早期发育的分子机制。这个 目标是确定特定基因在内皮细胞中的作用- 与心内膜垫形成相关的间质转变和 利用最近开发的一种鹌鹑心脏细胞系来寻找基因 参与调节心肌细胞的测定。调查人员 大学内部将整合他们的资源，使用标准动物 探索基本机制的模型和细胞培养技术 参与心肌肥大和衰竭。机制一直是 为数据交流、研究的批判性审查而设立 进度，以及对项目所有方面的行政控制。

This proposal is a multidisciplinary study of the cellular and biochemical basis for alterations int he mechanical performance of the hypertrophied and failing heart. Rat and rabbit post-infarction heart failure models will be studied. Emphasis is placed on thyroid hormone (T3)-induced hypertrophy because mechanical performance is enhanced, and insights gained into this form of hypertrophy may provide a rational basis for the development of T3 analogs as inotropic agents. In this renewal application, support is requested for five projects: 1) molecular basis for the control of myosin heavy chain expression, including the cloning and characterization of the regulatory proteins. 2) The role of the autonomic nervous system in the modulation of cardiac growth and performance. 3) The regulation of contraction in smooth muscle, particularly with respect to the role of phosphatases, in control of smooth muscle myosin phosphorylation. 4) A new project will be initiated on molecular mechanisms in early cardiac development. The objectives are to define the role of specific genes in endothelial- mesenchymal transitions associated with endocardial cushion formation and to use a recently developed quail heart cell line to search for genes involved in regulating myocardial cell determination. Investigators within the university will combine their resources, using standard animal models and cell culture techniques to explore fundamental mechanisms involved in cardiac hypertrophy and failure. Mechanisms have been established for communication of data, critical review of research progress, and administrative control of all aspects of the project.