CELLULAR MECHANISMS IN CARDIAC HYPERTROPHY

心脏肥大的细胞机制

• 批准号: 3097785
• 负责人: EUGENE MORKIN
• 金额: $ 70.06万
• 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/3097785
• 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.

本提案是一个多学科的研究细胞和