Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Schmidt, AG; Edes, I; Kranias, EG.
Phospholamban: a promising therapeutic target in heart failure?
Cardiovasc Drugs Ther. 2001; 15(5): 387-396.
Doi: 10.1023/A:1013381204658
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Schmidt Albrecht
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- Abstract:
- Dilated cardiomyopathy and end-stage heart failure result in characteristic functional, biochemical and molecular alterations. Multiple defects in cardiac excitation-contraction coupling have been suggested to underlie disturbed myocardial function and progressive remodeling. Ca2+ uptake and release by the sarcoplasmic reticulum (SR) have been shown to be altered in various animal models and human conditions. This review will focus on SR Ca2+ ATPase and its regulatory protein, phospholamban, as potential therapeutic targets. We summarize structural and genetic approaches, which have helped to elucidate the physiological role of phospholamban as a principal regulator of cardiac contractility and beta-adrenergic stimulation in the heart. These findings are extended to the clinical arena, indicating a phospholamban/SR Ca2+ ATPase mismatch in human heart failure. Evidence is then provided, using genetically engineered mouse models, that SR dysfunction may play a key role in the onset and progression of heart failure. Phospholamban deficiency may prevent such left ventricular dysfunction and its progression to heart failure in some of the animal models with dilated cardiomyopathy. Based on these findings, we discuss the question of whether and how interfering with the phospholamban/SR Ca2+ ATPase interaction may be a promising therapeutic approach for heart failure.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Calcium-Binding Proteins - genetics Calcium-Binding Proteins - physiology
- Calcium-Transporting ATPases - metabolism
- Cardiomyopathy, Dilated - genetics Cardiomyopathy, Dilated - metabolism Cardiomyopathy, Dilated - physiopathology
- Humans -
- Mice -
- Mice, Knockout -
- Myocardial Contraction - genetics Myocardial Contraction - physiology
- Sarcoplasmic Reticulum - enzymology Sarcoplasmic Reticulum - physiology
- Sarcoplasmic Reticulum Calcium-Transporting ATPases -
- Find related publications in this database (Keywords)
- heart
- calcium cycling
- sarcoplasmic reticulum
- phospholamban