Related Experiment Videos
Protein changes observed in pacing-induced heart failure using two-dimensional electrophoresis
M Y Heinke1, C H Wheeler, D Chang
1Muscle Research Unit, Institute of Biomedical Research, The University of Sydney, NSW, Australia. monique@anatomy.usyd.edu.au
Electrophoresis
|September 18, 1998
Summary
Rapid ventricular pacing in dogs creates a heart failure model. This study identified key protein changes in mitochondria and cytoskeleton, revealing mechanisms of pacing-induced cardiomyopathy.
Area of Science:
- Cardiovascular Physiology
- Proteomics
- Molecular Cardiology
Background:
- Rapid ventricular pacing in dogs induces a low-output cardiomyopathic state, mimicking human idiopathic dilated cardiomyopathy.
- The precise pathophysiological mechanisms underlying pacing-induced heart failure remain largely unknown.
Purpose of the Study:
- To investigate protein expression alterations in the left ventricular myocardium of dogs subjected to rapid ventricular pacing.
- To identify specific proteins and pathways involved in the development of pacing-induced cardiomyopathy.
Main Methods:
- Two-dimensional gel electrophoresis (2-DE) was employed to compare protein patterns between paced and control canine left ventricular samples.
- Protein expression changes were analyzed qualitatively and semi-quantitatively.
- Identified proteins were characterized using N-terminal sequencing, mass spectrometry, and database comparisons.
Main Results:
- A total of 69 protein spots showed significant alterations in paced dogs, with 42 decreased and 27 increased.
- Elongation factor Tu was uniquely absent in paced hearts.
- Ten identified proteins involved in mitochondrial energy production (e.g., pyruvate dehydrogenase, HSP60/70) and cytoskeletal proteins (e.g., desmin) exhibited altered expression.
Conclusions:
- Pacing-induced heart failure in dogs involves significant dysregulation of mitochondrial energy production pathways.
- Alterations in cytoskeletal protein expression, including desmin fragmentation, contribute to cardiac dysfunction.
- These findings highlight the roles of mitochondrial dysfunction, cytoskeletal instability, and calcium activation in the pathogenesis of this cardiomyopathy model.