CaMKII signaling in heart diseases: Emerging role in diabetic cardiomyopathy

Research output: Contribution to journalReview article

Abstract

Calcium/calmodulin-dependent protein kinase II (CaMKII) is upregulated in diabetes and significantly contributes to cardiac remodeling with increased risk of cardiac arrhythmias. Diabetes is frequently associated with atrial fibrillation, coronary artery disease, and heart failure, which may further enhance CaMKII. Activation of CaMKII occurs downstream of neurohormonal stimulation (e.g. via G-protein coupled receptors) and involve various posttranslational modifications including autophosphorylation, oxidation, S-nitrosylation and O-GlcNAcylation. CaMKII signaling regulates diverse cellular processes in a spatiotemporal manner including excitation-contraction and excitation-transcription coupling, mechanics and energetics in cardiac myocytes. Chronic activation of CaMKII results in cellular remodeling and ultimately arrhythmogenic alterations in Ca2+ handling, ion channels, cell-to-cell coupling and metabolism. This review addresses the detrimental effects of the upregulated CaMKII signaling to enhance the arrhythmogenic substrate and trigger mechanisms in the heart. We also briefly summarize preclinical studies using kinase inhibitors and genetically modified mice targeting CaMKII in diabetes. The mechanistic understanding of CaMKII signaling, cardiac remodeling and arrhythmia mechanisms may reveal new therapeutic targets and ultimately better treatment in diabetes and heart disease in general.

LanguageEnglish (US)
Pages246-259
Number of pages14
JournalJournal of Molecular and Cellular Cardiology
Volume127
DOIs
StatePublished - Feb 1 2019

Fingerprint

Diabetic Cardiomyopathies
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Heart Diseases
Cardiac Arrhythmias
Excitation Contraction Coupling
Calcium-Calmodulin-Dependent Protein Kinases
Post Translational Protein Processing
G-Protein-Coupled Receptors
Mechanics
Ion Channels
Cardiac Myocytes
Atrial Fibrillation
Coronary Artery Disease
Phosphotransferases
Heart Failure

Keywords

  • Arrhythmias
  • Calcium/calmodulin-dependent protein kinase II
  • Diabetes
  • Excitation-contraction coupling
  • Heart
  • Posttranslational modifications

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

CaMKII signaling in heart diseases : Emerging role in diabetic cardiomyopathy. / Hegyi, Bence; Bers, Donald M; Bossuyt, Julie B C.

In: Journal of Molecular and Cellular Cardiology, Vol. 127, 01.02.2019, p. 246-259.

Research output: Contribution to journalReview article

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