title: The promise of CaMKII inhibition for heart disease: preventing heart failure and arrhythmias.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of California, Department of Pharmacology, San Diego, La Jolla, CA, USA.
authors.forename: B Daan
authors.initials: BD
authors.lastname: Westenbrink
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Edwards
authors.forename: Andrew D
authors.initials: AD
authors.lastname: McCulloch
authors.forename: Joan Heller
authors.initials: JH
authors.lastname: Brown
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors* / Q000502:physiology; D006331:Heart Diseases / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium