CELLULAR MECHANISMS IN CARDIAC HYPERTROPY

心脏肥大的细胞机制

• 批准号: 2215408
• 负责人: EUGENE MORKIN
• 金额: $ 76.37万
• 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 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2215408
• 关键词: cellular pathology; heart enlargement; heart failure

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.

本提案是一个多学科的研究细胞和