The objective of this proposal is to define the alterations in myocardial protein metabolism that regulate the responses to acute and chronic volume overload in an intact animal model of aortic regurgitation. The relative contributions of cardiac protein synthesis and degradation to the structural remodelling that occurs during the development of left ventricular dilatation and eccentric hypertrophy will be examined. The effects of the severity and chronicity of volume overload on synthesis and degradation rates of total cardiac protein, individual myofibrillar proteins and collagen will be investigated. The hypothesis to be tested is that specific and total cardiac protein degradation rates as well as synthesis rates are fundamentally important to the regulation of cardiac protein mass during the left ventricular dilation and eccentric hypertrophy that develop in response to chronic volume overload. Thus we will examine the biochemical mechanisms underlying the structural and functional responses to chronic aortic regurgitation. The process of testing our hypothesis can be expected to improve understanding of cardiac protein regulation in vivo. Specifically, it is hoped that these studies may allow identification of protein metabolic abnormalities that could prove useful as indices of degeneration for timing of valve replacement, or which might provide insights helpful in the design of new therapeutic approaches to retarding the effects of volume loading.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL040679-03
Application #
3472107
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1988-04-01
Project End
1993-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065
Borer, Jeffrey S; Sharma, Abhishek (2015) Drug Therapy for Heart Valve Diseases. Circulation 132:1038-45
Borer, Jeffrey S; Truter, Sharada L; Gupta, Anuj et al. (2004) Heart failure in aortic regurgitation: the role of primary fibrosis and its cellular and molecular pathophysiology. Adv Cardiol 41:16-24
King, R K; Magid, N M; Opio, G et al. (1997) Protein turnover in compensated chronic aortic regurgitation. Cardiology 88:518-25
Lu, P; Zanzonico, P; Goldfine, S M et al. (1997) Antimyosin antibody imaging in experimental aortic regurgitation. J Nucl Cardiol 4:25-32
Magid, N M; Opio, G; Wallerson, D C et al. (1994) Heart failure due to chronic experimental aortic regurgitation. Am J Physiol 267:H556-62
Magid, N M; Wallerson, D C; Borer, J S (1993) Myofibrillar protein turnover in cardiac hypertrophy due to aortic regurgitation. Cardiology 82:20-9
Magid, N M; Borer, J S; Young, M S et al. (1993) Suppression of protein degradation in progressive cardiac hypertrophy of chronic aortic regurgitation. Circulation 87:1249-57
Okin, P M; Donnelly, T M; Parker, T S et al. (1992) High-frequency analysis of the signal-averaged ECG. Correlation with left ventricular mass in rabbits. J Electrocardiol 25:111-8
Magid, N M; Wallerson, D C; Borer, J S et al. (1992) Left ventricular diastolic and systolic performance during chronic experimental aortic regurgitation. Am J Physiol 263:H226-33