Sarcomeric dysfunction in heart failure

N Hamdani, V Kooij, S van Dijk, Daphne Merkus, WJ Paulus, C dos Remedios, Dirk-jan Duncker, GJM Stienen, J Velden

Research output: Contribution to journalReview articleAcademicpeer-review

150 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)649-658
Number of pages10
JournalCardiovascular Research
Volume77
Issue number4
DOIs
Publication statusPublished - 2008

Research programs

  • EMC COEUR-01-43-01

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