Protein changes observed in pacing-induced heart failure using two-dimensional electrophoresis.
Rapid ventricular pacing in dogs results in a low output cardiomyopathic state which is similar to idiopathic dilated cardiomyopathy in man. However, the pathophysiological mechanisms which cause this failure following pacing are unknown. Five dogs underwent rapid ventricular pacing. Hearts were stimulated at 245 beats per min (bpm) for four weeks and then reduced to 190 bpm to stabilize the failure. Six unoperated dogs were used as controls. This paper compares the two-dimensional gel electrophoresis (2-DE) protein patterns of left ventricular samples from the paced myocardium with the control dogs. Changes in protein expression were analyzed qualitatively and semi-quantitatively. In the paced dog samples 69 protein spots were significantly altered of which 42 were decreased and 27 were elevated. One qualitative change was observed: elongation factor Tu was present only the control hearts. Of these proteins, 20 have been identified by a combination of N-terminal protein microsequencing, peptide mass profiling by mass spectrometry, amino acid compositional analysis, and by comparison with databases of canine and human ventricular proteins. Ten of these are associated with mitochondria and energy production, including: pyruvate dehydrogenase E1 component, isocitrate dehydrogenase subunit alpha, HSP60 and HSP70, creatine kinase M and fatty acid binding protein. The cytoskeletal protein desmin was detected in reduced quantities and a spot corresponding to a fragment of desmin was increased. These results indicate that the development of heart failure in the paced dog involves alterations in mitochondrial energy production, the cytoskeleton and calcium activation.
Heinke
M Y
MY
Muscle Research Unit, Institute of Biomedical Research, The University of Sydney, NSW, Australia. monique@anatomy.usyd.edu.au
Wheeler
C H
CH
Chang
D
D
Einstein
R
R
Drake-Holland
A
A
Dunn
M J
MJ
dos Remedios
C G
CG
D000818:Animals; D002304:Cardiac Pacing, Artificial; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006352:Heart Ventricles; D006801:Humans; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*
D011506:Proteins