Publication

The promise of CaMKII inhibition for heart disease: preventing heart failure and arrhythmias

Westenbrink, B. D., Edwards, A. G., McCulloch, A. D. & Brown, J. H., Aug-2013, In : EXPERT OPINION ON THERAPEUTIC TARGETS. 17, 8, p. 889-903 15 p.

Research output: Contribution to journalReview articleAcademicpeer-review

Introduction: Calcium-calmodulin-dependent protein kinase II (CaMKII) has emerged as a central mediator of cardiac stress responses which may serve several critical roles in the regulation of cardiac rhythm, cardiac contractility and growth. Sustained and excessive activation of CaMKII during cardiac disease has, however, been linked to arrhythmias, and maladaptive cardiac remodeling, eventually leading to heart failure (HF) and sudden cardiac death.

Areas covered: In the current review, the authors describe the unique structural and biochemical properties of CaMKII and focus on its physiological effects in cardiomyocytes. Furthermore, they provide evidence for a role of CaMKII in cardiac pathologies, including arrhythmogenesis, myocardial ischemia and HF development. The authors conclude by discussing the potential for CaMKII as a target for inhibition in heart disease.

Expert opinion: CaMKII provides a promising nodal point for intervention that may allow simultaneous prevention of HF progression and development of arrhythmias. For future studies and drug development there is a strong rationale for the development of more specific CaMKII inhibitors. In addition, an improved understanding of the differential roles of CaMKII subtypes is required.

Original languageEnglish
Pages (from-to)889-903
Number of pages15
JournalEXPERT OPINION ON THERAPEUTIC TARGETS
Volume17
Issue number8
Publication statusPublished - Aug-2013

    Keywords

  • arrhythmia, CaMKII, heart failure, ischemia, mitochondria, PROTEIN-KINASE-II, CARDIAC RYANODINE RECEPTOR, RAT VENTRICULAR MYOCYTES, NUCLEAR DELTA(B) ISOFORM, RETICULUM CALCIUM LEAK, OUTWARD K+ CURRENT, CALMODULIN KINASE, SARCOPLASMIC-RETICULUM, NA+ CHANNEL, DILATED CARDIOMYOPATHY

ID: 5916104