CELLULAR MECHANISMS IN CARDIAC HYPERTROPHY

这项提案是对细胞和 机械性能改变的生物化学基础 肥大和衰竭的心脏。几个动物模型将 被研究，包括大鼠梗死后心力衰竭模型， 自发性高血压大鼠，和小鼠模型 柯萨奇乙型病毒性心肌炎。在此续期申请中，我们将 我们的研究主要集中在五个方面：1)分子 肌球蛋白重链基因表达的调控机制 包括甲状腺激素和机械拉伸的影响。 2)自主神经系统和其他神经体液的作用 心脏生长和性能调节中的因素。3) 对血管平滑肌收缩的调节作用 强调平滑肌的结构-功能关系 肌球蛋白和肌球蛋白轻链激酶。4)治疗方法的比较 使用类甲状腺药物与更传统的治疗相比， 用大鼠脑梗塞后心力衰竭模型验证这一假说 从低活性心肌肌球蛋白亚型转换到高活性肌球蛋白亚型 在心力衰竭的治疗中可能是一种有价值的策略。 5)细胞免疫在小鼠柯萨奇B组病毒感染中的作用 将对心肌炎进行调查，目标是开发一种 为治疗人病毒性心肌炎提供合理依据。 该机构内部的调查人员将整合他们的资源， 利用常见动物模型探索基本机制 与肥大和衰竭有关。这项提议代表着 继续开展已经在进行的合作努力 各种实验室。已经为以下方面建立了机制 数据沟通，正在进行的研究的批判性审查和 对这个项目的所有方面进行行政控制。

This proposal is a multidisciplinary study of the cellular and biochemical basis for alterations in the mechanical performance of the hypertrophied and failing hearts. Several animals models will be studied, including the rat post-infarction heart failure model, the spontaneously hypertensive rat, and a mouse model of Coxsackievirus B myocarditis. In this renewal application, we will focus our investigations on five general areas: 1) Molecular mechanisms in the regulation of myosin heavy chain gene_expression, including the effects of thyroid hormone and mechanical stretch. 2) The role of the autonomic nervous system and other neurohumoral factors in the modulation of cardiac growth and performance. 3) The regulation of contraction in vascular smooth muscle with emphasis on structure-function relationships in smooth muscle myosin and myosin light chain kinase. 4) Comparison of treatment with thyromimetic agents versus more conventional therapy in the rat post-infarction heart failure model to examine the hypothesis that switching from a low to a high activity cardiac myosin isoform might be a worthwhile strategy in the management of heart failure. 5) The role of cell- mediated immunity in murine Coxsackievirus B myocarditis will be investigated with the goal of developing a rational basis for treatment of human viral myocarditis. Investigators within the institution will combine their resources, using common animal models to explore fundamental mechanisms involved in hypertrophy and failure. This proposal represents a continuation of collaborative efforts that already are underway in various laboratories. Mechanisms have been established for communication of data, critical review of research in progress and administrative control of all aspects of this project.