CELLULAR MECHANISMS IN CARDIAC HYPERTROPHY

心脏肥大的细胞机制

• 批准号: 3097784
• 负责人: EUGENE MORKIN
• 金额: $ 64.56万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-09-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3097784
• 关键词: cellular pathology; heart enlargement; heart failure; muscle proteins; myosin light chain kinase; neuropeptides

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.

这项建议是一个多学科的研究细胞和 生物化学基础的机械性能的改变 心脏肥大衰竭 几种动物模型将 包括大鼠心肌梗死后心力衰竭模型， 自发性高血压大鼠和小鼠模型 柯萨奇病毒B心肌炎。 在此更新申请中，我们将 我们的研究集中在五个一般领域：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 调节心脏生长和性能的因素。 第三章 血管平滑肌收缩的调节 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)比较治疗 拟甲状腺药物与常规治疗相比， 大鼠梗死后心力衰竭模型来检验假设 从低活性到高活性的心肌肌球蛋白亚型 可能是治疗心力衰竭的一个有价值的策略。 5)细胞免疫在小鼠柯萨奇病毒B感染中的作用 将对心肌炎进行调查，目的是制定一项 为治疗人类病毒性心肌炎提供了合理依据。 机构内的调查人员将联合收割机整合他们的资源， 使用普通动物模型探索基本机制 与肥大和衰竭有关 该提案代表了 继续进行已经在进行的合作努力， 各种实验室。 已建立机制， 交流数据，对正在进行的研究进行严格审查， 对该项目的各个方面进行管理。