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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL020984-19
Application #
2215409
Study Section
Heart, Lung, and Blood Research Review Committee A (HLBA)
Project Start
1977-09-01
Project End
1998-08-31
Budget Start
1995-09-01
Budget End
1996-08-31
Support Year
19
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Arizona
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Wilund, Kenneth R; Yu, Liqing; Xu, Fang et al. (2004) No association between plasma levels of plant sterols and atherosclerosis in mice and men. Arterioscler Thromb Vasc Biol 24:2326-32
Porter, Amy C; Svensson, Samuel P S; Stamer, W Daniel et al. (2003) Alpha-2 adrenergic receptors stimulate actin organization in developing fetal rat cardiac myocytes. Life Sci 72:1455-66
Cottin, P; Thompson, V F; Sathe, S K et al. (2001) Autolysis of mu- and m-calpain from bovine skeletal muscle. Biol Chem 382:767-76
Adamson, C; Niu, S; Bahl, J J et al. (2001) Cloning and characterization of P110, a novel small nucleolar U3 ribonucleoprotein, expressed in early development. Exp Cell Res 263:55-64
Maitra, N; Flink, I L; Bahl, J J et al. (2000) Expression of alpha and beta integrins during terminal differentiation of cardiomyocytes. Cardiovasc Res 47:715-25
Spooner, P H; Morkin, E; Goldman, S (1999) Thyroid hormone and thyroid hormone analogues in the treatment of heart failure. Coron Artery Dis 10:395-9
Feng, J; Ito, M; Kureishi, Y et al. (1999) Rho-associated kinase of chicken gizzard smooth muscle. J Biol Chem 274:3744-52
Feng, J; Ito, M; Nishikawa, M et al. (1999) Dephosphorylation of distinct sites on the 20 kDa myosin light chain by smooth muscle myosin phosphatase. FEBS Lett 448:101-4
Boyer, A S; Ayerinskas, I I; Vincent, E B et al. (1999) TGFbeta2 and TGFbeta3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart. Dev Biol 208:530-45
Niu, S; Bahl, J J; Adamson, C et al. (1998) Structure, regulation and function of avian glypican. J Mol Cell Cardiol 30:537-50

Showing the most recent 10 out of 171 publications