Myofibrillar protein turnover in cardiac hypertrophy due to aortic regurgitation.
We recently demonstrated that total cardiac protein and myosin heavy chain fractional synthesis rates were not increased during the progressive cardiac hypertrophy that occurred 1 month following induction of aortic regurgitation. The increase in total cardiac protein and myosin heavy chain observed after 1 month of chronic volume overload was caused by a decrease in protein fractional degradation rates. The objective of the present study was to determine in vivo the relative contributions of protein synthesis and degradation of a variety of individual myofibrillar protein constituents, other than myosin heavy chain, to the left ventricular hypertrophic response to chronic aortic regurgitation. Intravenous infusions of [3H]-leucine were administered 3 days and 1 month following surgical induction of aortic regurgitation and sham operation in rabbits, and actin, myosin light chains 1 and 2, alpha-actinin and desmin fractional synthesis rates were obtained by analysis of plasma and protein hydrolysate data using [14C]-dansyl chloride assays. Individual myofibrillar protein growth rates were determined from protein concentration and serial echocardiographic and postmortem left ventricular weight measurements; protein degradation rates were determined by subtraction of growth rates from synthesis rates. Individual myofibrillar protein content increased most rapidly during the 1st week and progressively increased at a slower rate between 1 week and 1 month, in parallel with increases in left ventricular weight. In comparison with sham-operated controls, individual myofibrillar protein fractional synthesis rates were consistently increased at 3 days but not at 1 month. Progressive myocyte hypertrophy occurring at 1 month was caused by a decrease in myofibrillar protein fractional degradation rates. Increased myofibrillar protein synthesis contributed only to the early phase of myocyte hypertrophy while progressive hypertrophy in chronic aortic regurgitation was due to suppression of myofibrillar protein degradation.
Magid
N M
NM
Department of Medicine, Cornell University Medical College, New York Hospital-Cornell Medical Center, N.Y. 10021.
Wallerson
D C
DC
Borer
J S
JS
D000199:Actins / Q000378:metabolism; D000818:Animals; D001022:Aortic Valve Insufficiency / Q000473:pathology*; D001810:Blood Volume / Q000502:physiology; D002148:Calmodulin-Binding Proteins; D003893:Desmin / Q000378:metabolism; D006333:Heart Failure / Q000473:pathology*; D006352:Heart Ventricles / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000473:pathology*; D009124:Muscle Proteins / Q000378:metabolism*; D009206:Myocardium / Q000473:pathology; D009210:Myofibrils / Q000648:ultrastructure; D011506:Proteins / Q000378:metabolism*; D011817:Rabbits
D000199:Actins; D002148:Calmodulin-Binding Proteins; D003893:Desmin; D009124:Muscle Proteins; D011506:Proteins