Sarcomeric dysfunction in heart failure

Sarcomeric dysfunction plays a central role in reduced cardiac pump function in heart failure. This review focuses on the alterations in sarcomeric proteins in diseased myocardium that range from altered isoform expression to post-translational protein changes such as proteolysis and phosphorylation...

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Bibliographic Details
Published in:Cardiovascular research 2008-03, Vol.77 (4), p.649-658
Main Authors: Hamdani, Nazha, Kooij, Viola, van Dijk, Sabine, Merkus, Daphne, Paulus, Walter J., Remedios, Cris dos, Duncker, Dirk J., Stienen, Ger J.M., van der Velden, Jolanda
Format: Article
Language:English
Subjects:
Animals
Cardiomyocyte
Contractility
Heart failure
Heart Failure - metabolism
Heart Failure - pathology
Heart Failure - physiopathology
Humans
Muscle Proteins - metabolism
Myocardial Contraction
Myocardium - metabolism
Myocardium - pathology
Peptide Hydrolases - metabolism
Phosphorylation
Protein Isoforms
Protein Kinases - metabolism
Protein Processing, Post-Translational
Sarcomere
Sarcomeres - metabolism
Sarcomeres - pathology
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Summary:Sarcomeric dysfunction plays a central role in reduced cardiac pump function in heart failure. This review focuses on the alterations in sarcomeric proteins in diseased myocardium that range from altered isoform expression to post-translational protein changes such as proteolysis and phosphorylation. Recent studies in animal models of heart failure and human failing myocardium converge and indicate that sarcomeric dysfunction, including altered maximum force development, Ca2+ sensitivity, and increased passive stiffness, largely originates from altered protein phosphorylation, caused by neurohumoral-induced alterations in the kinase–phosphatase balance inside the cardiomyocytes. Novel therapies, which specifically target phosphorylation sites within sarcomeric proteins or the kinases and phosphatases involved, might improve cardiac function in heart failure.
ISSN:0008-6363
1755-3245
DOI:10.1093/cvr/cvm079