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Sarcoplasmic reticulum proteins in heart failure.
S E Lehnart1, W Schillinger, B Pieske
1Medizinische Klinik III, Universität Freiburg, Germany.
Annals of the New York Academy of Sciences
|December 22, 1999
Summary
Altered calcium handling proteins, sarcoplasmic reticulum calcium ATPase (SR-Ca2+-ATPase) and sodium-calcium exchanger, are implicated in human heart failure. Their dysregulation impacts both systolic and diastolic heart function.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Altered calcium homeostasis is a key factor in human heart failure pathophysiology.
- Specific protein alterations in calcium handling pathways are suspected contributors.
Purpose of the Study:
- To analyze sarcoplasmic reticulum (SR) protein levels and sarcolemmal Na(+)-Ca2+ exchanger in failing and nonfailing human myocardium.
- To correlate these protein levels with myocardial function.
Main Methods:
- Western blot analysis was used to quantify protein levels in human heart samples.
- Protein levels were compared between failing and nonfailing hearts.
- Correlations between protein levels and functional parameters (systolic and diastolic forces) were assessed.
Main Results:
- SR calcium release channel, calsequestrin, and calreticulin levels were unchanged.
- SR-Ca(2+)-ATPase levels and its ratio to phospholamban were decreased in failing hearts.
- Na(+)-Ca2+ exchanger levels and its ratio to SR-Ca(2+)-ATPase were increased in failing hearts.
- SR-Ca(2+)-ATPase levels correlated with systolic function.
- Na(+)-Ca2+ exchanger levels correlated inversely with diastolic function.
Conclusions:
- Downregulation of SR-Ca(2+)-ATPase and upregulation of Na(+)-Ca2+ exchanger contribute to impaired systolic and diastolic function in human heart failure.
- These specific protein alterations are significant in the pathophysiology of heart failure.