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Myosin isoenzymes in normal and hypertrophied human hearts
Insights
Human heart myosin isoforms differ between atria and ventricles, changing with development and disease. Ventricular myosin shifts to an atrial type in hypertrophic or infarcted hearts, indicating significant cardiac remodeling.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Biochemistry
Background:
- Myosin, a key contractile protein, exists in various isoforms with distinct functional properties.
- Understanding myosin isoform distribution is crucial for diagnosing and treating cardiac diseases.
Purpose of the Study:
- To identify and characterize distinct myosin isoforms in human heart ventricles and atria.
- To investigate changes in myosin composition during fetal development, normal conditions, and cardiac hypertrophy/infarction.
Main Methods:
- Analytical ultracentrifugation
- Ca2+-dependent ATPase assays
- Enzyme activity measurements (temperature dependence)
- SDS-polyacrylamide gel electrophoresis
- Isoelectric focusing
- Pyrophosphate gel electrophoresis
Main Results:
- Ventricle and atrium myosins are indistinguishable by sedimentation but differ in Ca2+-dependent ATPase and activation parameters.
- A fetal light chain and an additional faster-migrating foetal isomyosin were identified in ventricular tissue.
- Normal atria contain two distinct myosin isoforms (HA-3, HA-1) and ventricular isomyosin.
- Hypertrophic atria show a marked increase in ventricular isomyosin proportion.
- Normal ventricles typically exhibit one isoenzyme; however, myocardial infarction induces a shift towards atrial myosin type.
Conclusions:
- Human cardiac myosin isoforms exhibit tissue-specific and developmental regulation.
- Cardiac disease states like hypertrophy and myocardial infarction lead to significant alterations in ventricular myosin heavy chain composition.
- These myosin isoform shifts reflect adaptive or pathological remodeling in the human heart.
Abstract:
Distinct myosin isoforms were identified from the ventricles and atria of foetal, normal and hypertrophied human hearts. Ventricle and atrium myosins cannot be differentiated by their sedimentation behaviour in the analytical ultracentrifuge, they vary, however, with regard to the Ca2+-dependent ATPase and also the activation parameters in measurements of the enzyme activity in dependence on temperature. In agreement with other authors we observed a foetal light chain in the ventricular tissue of the latter half of gestation, when myosin was characterized by SDS-polyacrylamide gel electrophoresis and isoelectric focusing. Using pyrophosphate gel electrophoresis an additional foetal isomyosin was observed besides the typical ventricular myosin HV-3, which migrates faster. Two distinct myosin isoforms designated as HA-3 and HA-1 occur in the atrium of the normal human heart. It was found that besides their own isoenzymes normal atria also contain ventricular isomyosin, whose relative proportion is markedly increased in the hypertrophic atrium. In contrast, we usually observed only one isoenzyme in the normal ventricle. Moreover, in case of myocardial infarction a dramatic transformation of myosin heavy chain composition with a shift to an atrial myosin type took place in the ventricle.