| Phospholamban: a promising therapeutic target in heart failure? | |
| | |
MedLine Citation:
|
PMID: 11855657 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
A G Schmidt; I Edes; E G Kranias |
Related Documents
:
|
8062417 - Relation between myocardial function and expression of sarcoplasmic reticulum ca(2+)-at... 18096697 - A single luminally continuous sarcoplasmic reticulum with apparently separate ca2+ stor... 17052727 - Camkii inhibition targeted to the sarcoplasmic reticulum inhibits frequency-dependent a... 2579587 - Ca influx and sarcoplasmic reticulum ca release in cardiac muscle activation during pos... 20445047 - Two slow calcium-activated afterhyperpolarization currents control burst firing dynamic... 15972387 - Activation of nad(p)h oxidase by outward movements of h+ ions in renal medullary thick ... |
Publication Detail:
|
Type: Journal Article; Review |
Journal Detail:
|
Title: Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy Volume: 15 ISSN: 0920-3206 ISO Abbreviation: Cardiovasc Drugs Ther Publication Date: 2001 Sep |
Date Detail:
|
Created Date: 2002-02-21 Completed Date: 2002-07-29 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 8712220 Medline TA: Cardiovasc Drugs Ther Country: United States |
Other Details:
|
Languages: eng Pagination: 387-96 Citation Subset: IM |
Affiliation:
|
Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, OH 45267, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Calcium-Binding Proteins / genetics, physiology* Calcium-Transporting ATPases / metabolism* Cardiomyopathy, Dilated / genetics, metabolism, physiopathology* Humans Mice Mice, Knockout Myocardial Contraction / genetics, physiology* Sarcoplasmic Reticulum / enzymology, physiology* Sarcoplasmic Reticulum Calcium-Transporting ATPases |
| Chemical | |
Reg. No./Substance:
|
0/Calcium-Binding Proteins; 0/phospholamban; EC 3.6.1.8/Calcium-Transporting ATPases; EC 3.6.3.8/Sarcoplasmic Reticulum Calcium-Transporting ATPases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Na+ channel activators as positive inotropic agents for the treatment of chronic heart failure.
Next Document: Mechanism of action of Ca2+ sensitizers--update 2001.