CELLULAR MECHANISMS IN CARDIAC HYPERTROPY

这项建议是一个多学科的研究细胞和 生物化学的基础上改变他的机械性能， 心脏肥大和衰竭 大鼠和家兔梗死后心脏 将研究故障模式。 重点放在甲状腺激素上 （T3）-诱导的肥大，因为机械性能增强，和 对这种形式的肥大的深入了解可能会提供一个合理的 T3类似物作为变力剂的发展基础。 在这 更新申请，要求支持五个项目：1） 控制肌球蛋白重链表达的分子基础， 包括调控蛋白的克隆和表征。 2)自主神经系统在心脏电活动调节中的作用 增长和业绩。 3)平滑肌收缩的调节 肌肉，特别是磷酸酶的作用， 平滑肌肌球蛋白磷酸化。 4)一个新的项目将是 心脏发育早期的分子机制。 的 目的是确定特定基因在内皮- 与内膜垫形成相关的间充质转化， 利用最近开发的鹌鹑心脏细胞系来寻找基因 参与调节心肌细胞的决定。 调查人员 将联合收割机他们的资源，使用标准动物 模型和细胞培养技术来探索基本机制 与心脏肥大和衰竭有关 机制已经 为交流数据、对研究进行严格审查而设立 进度和项目各方面的行政控制。

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.