Abstract:
:Understanding relationships between heart failure and arrhythmias, important causes of suffering and sudden death, remains an unmet goal for biomedical researchers and physicians. Evidence assembled over the past decade supports a view that activation of the multifunctional Ca(2+) and calmodulin-dependent protein kinase II (CaMKII) favors myocardial dysfunction and cell membrane electrical instability. CaMKII activation follows increases in intracellular Ca(2+) or oxidation, upstream signals with the capacity to transition CaMKII into a Ca(2+) and calmodulin-independent constitutively active enzyme. Constitutively active CaMKII appears poised to participate in disease pathways by catalyzing the phosphorylation of classes of protein targets important for excitation-contraction coupling and cell survival, including ion channels and Ca(2+) homeostatic proteins, and transcription factors that drive hypertrophic and inflammatory gene expression. This rich diversity of downstream targets helps to explain the potential for CaMKII to simultaneously affect mechanical and electrical properties of heart muscle cells. Proof-of-concept studies from a growing number of investigators show that CaMKII inhibition is beneficial for improving myocardial performance and for reducing arrhythmias. We review the molecular physiology of CaMKII and discuss CaMKII actions at key cellular targets and results of animal models of myocardial hypertrophy, dysfunction, and arrhythmias that suggest CaMKII inhibition may benefit myocardial function while reducing arrhythmias.
journal_name
Circ Resjournal_title
Circulation researchauthors
Swaminathan PD,Purohit A,Hund TJ,Anderson MEdoi
10.1161/CIRCRESAHA.111.243956subject
Has Abstractpub_date
2012-06-08 00:00:00pages
1661-77issue
12eissn
0009-7330issn
1524-4571pii
110/12/1661journal_volume
110pub_type
杂志文章,评审abstract::Arteries from deoxycorticosterone acetate (DOCA)-salt and N(omega)-nitro-L-arginine (L-NNA) hypertensive but not normotensive rats develop spontaneous tone. LY294002 and wortmannin, phosphoinositide 3-kinase (PI3-kinase) inhibitors, eliminate spontaneous tone. We hypothesized that PI3-kinase protein and/or activity wa...
journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2002-08-23 00:00:00
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journal_title:Circulation research
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.2.478
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pub_type: 杂志文章
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更新日期:2001-11-23 00:00:00
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更新日期:1990-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.50.5.671
更新日期:1982-05-01 00:00:00
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更新日期:1990-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:1996-01-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.5.1134
更新日期:1990-11-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.3.456
更新日期:1992-03-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1997-04-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.41.2.172
更新日期:1977-08-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000207407.51752.3c
更新日期:2006-03-17 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000160609.98948.25
更新日期:2005-04-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.316063
更新日期:2020-02-28 00:00:00
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pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.160176
更新日期:2008-02-15 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.164145
更新日期:2008-02-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.41.5.635
更新日期:1977-11-01 00:00:00
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更新日期:1994-10-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2009-09-11 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1987-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:2007-12-07 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2004-07-23 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2015-04-10 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1978-07-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.304382
更新日期:2014-09-26 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.77.4.832
更新日期:1995-10-01 00:00:00