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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL020984-15
Application #
3097784
Study Section
Heart, Lung, and Blood Research Review Committee A (HLBA)
Project Start
1977-09-01
Project End
1993-08-31
Budget Start
1991-09-21
Budget End
1992-08-31
Support Year
15
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Arizona
Department
Type
Schools of Medicine
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85721
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