PMID- 30633874
OWN - NLM
STAT- MEDLINE
DCOM- 20200108
LR  - 20200214
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Linking)
VI  - 127
DP  - 2019 Feb
TI  - CaMKII signaling in heart diseases: Emerging role in diabetic cardiomyopathy.
PG  - 246-259
LID - S0022-2828(19)30009-4 [pii]
LID - 10.1016/j.yjmcc.2019.01.001 [doi]
AB  - 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 Ca(2+) 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.
CI  - Copyright (c) 2019. Published by Elsevier Ltd.
FAU - Hegyi, Bence
AU  - Hegyi B
AD  - Department of Pharmacology, University of California Davis, Davis, CA, USA.
FAU - Bers, Donald M
AU  - Bers DM
AD  - Department of Pharmacology, University of California Davis, Davis, CA, USA. 
      Electronic address: dmbers@ucdavis.edu.
FAU - Bossuyt, Julie
AU  - Bossuyt J
AD  - Department of Pharmacology, University of California Davis, Davis, CA, USA.
LA  - eng
GR  - P01 HL080101/HL/NHLBI NIH HHS/United States
GR  - R01 HL030077/HL/NHLBI NIH HHS/United States
GR  - R01 HL142282/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20190108
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Ion Channels)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/chemistry/*metabolism
MH  - Diabetic Cardiomyopathies/*enzymology
MH  - Humans
MH  - Ion Channels/metabolism
MH  - Mitochondria, Heart/metabolism
MH  - *Signal Transduction
OTO - NOTNLM
OT  - Arrhythmias
OT  - Calcium/calmodulin-dependent protein kinase II
OT  - Diabetes
OT  - Excitation-contraction coupling
OT  - Heart
OT  - Posttranslational modifications
EDAT- 2019/01/12 06:00
MHDA- 2020/01/09 06:00
CRDT- 2019/01/12 06:00
PHST- 2018/12/27 00:00 [received]
PHST- 2019/01/04 00:00 [accepted]
PHST- 2019/01/12 06:00 [pubmed]
PHST- 2020/01/09 06:00 [medline]
PHST- 2019/01/12 06:00 [entrez]
AID - S0022-2828(19)30009-4 [pii]
AID - 10.1016/j.yjmcc.2019.01.001 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2019 Feb;127:246-259. doi: 10.1016/j.yjmcc.2019.01.001. Epub 
      2019 Jan 8.