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Calcium transport proteins in the nonfailing and failing heart: gene expression and function
1INSERM Unité 153, Pavillon Rambuteau, Hôpital Pitié-Salpétriere, Paris, France.
Insights
Heart failure involves abnormal intracellular calcium (Ca2+) handling, impacting heart muscle function. This review examines key proteins like the sarcoplasmic reticulum Ca2+-ATPase and Na+/Ca2+ exchanger in heart failure pathophysiology.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Intracellular Ca2+ handling is crucial for cardiomyocyte contraction and relaxation.
- Alterations in Ca2+ handling, including reduced peak transients and prolonged diastolic decline, characterize heart failure.
- Proteins of the sarcoplasmic reticulum and sarcolemmal Na+/Ca2+ exchanger are key regulators of Ca2+ homeostasis.
Purpose of the Study:
- To review the current understanding of proteins involved in myocardial Ca2+ handling.
- To explore expressional and functional alterations of these proteins in heart failure.
- To discuss the potential implications of these alterations in the pathomechanism of heart failure.
Main Methods:
- Review of existing scientific literature on Ca2+ handling proteins in heart failure.
- Analysis of studies investigating gene expression and protein function in failing myocardium (both experimental and human).
- Synthesis of findings regarding quantitative changes in sarcoplasmic reticulum Ca2+-ATPase, ryanodine receptor, and Na+/Ca2+ exchanger.
Main Results:
- Quantitative changes in the expression of key Ca2+ handling proteins have been reported in failing hearts.
- Correlations between altered protein expression and functional deficits in contraction and relaxation have been observed.
- Contradictory findings exist in human heart failure, necessitating further investigation.
Conclusions:
- Dysregulation of myocardial Ca2+ handling proteins is implicated in heart failure pathophysiology.
- Understanding these alterations is critical for developing targeted therapies.
- Further research is needed to resolve discrepancies in findings related to human heart failure.
Abstract:
In heart failure alterations of intracellular Ca2+ handling are thought to be a major reason for impaired contraction and relaxation. Peak Ca2+ transients are reduced, resting Ca2+ levels elevated, and the time course of diastolic Ca2+ decline is markedly prolonged in failing hearts. The proteins of the sarcoplasmic reticulum and the sarcolemmal Na+/Ca2+ exchanger are the most important tools for Ca2+ homeostasis in the cardiomyocyte, and their molecular cloning has allowed prediction of structure/function analysis. The investigation of function and gene expression of these proteins in failing myocardium has been an area of intensive research in recent years in order to provide a more detailed understanding of the pathophysiology of heart failure. Quantitative changes in expression of the sarcoplasmic reticulum Ca(2+)-ATPase, the ryanodine receptor, and the Na+/Ca2+ exchanger with correlations to functional alterations have been reported both in experimental animal models and in the human failing heart. However, in human heart failure these findings are currently the subject of a lively discussion because observations have apparently been in part contradictory. This review discusses the proteins involved in myocardial Ca2+ handling and describes the current state of research on expressional and functional alterations and their potential implication in the pathomechanism of heart failure.