Journal article
Oxidized Ca2+/Calmodulin-Dependent Protein Kinase II Triggers Atrial Fibrillation
Circulation (New York, N.Y.), Vol.128(16), pp.1748-1757
10/15/2013
DOI: 10.1161/CIRCULATIONAHA.113.003313
PMID: 24030498
Abstract
BACKGROUND—Atrial fibrillation (AF) is a growing public health problem without adequate therapies. Angiotensin II and reactive oxygen species are validated risk factors for AF in patients, but the molecular pathways connecting reactive oxygen species and AF are unknown. The Ca/calmodulin-dependent protein kinase II (CaMKII) has recently emerged as a reactive oxygen species–activated proarrhythmic signal, so we hypothesized that oxidized CaMKIIδ could contribute to AF.
METHODS AND RESULTS—We found that oxidized CaMKII was increased in atria from AF patients compared with patients in sinus rhythm and from mice infused with angiotensin II compared with mice infused with saline. Angiotensin II–treated mice had increased susceptibility to AF compared with saline-treated wild-type mice, establishing angiotensin II as a risk factor for AF in mice. Knock-in mice lacking critical oxidation sites in CaMKIIδ (MM-VV) and mice with myocardium-restricted transgenic overexpression of methionine sulfoxide reductase A, an enzyme that reduces oxidized CaMKII, were resistant to AF induction after angiotensin II infusion.
CONCLUSIONS—Our studies suggest that CaMKII is a molecular signal that couples increased reactive oxygen species with AF and that therapeutic strategies to decrease oxidized CaMKII may prevent or reduce AF.
Details
- Title: Subtitle
- Oxidized Ca2+/Calmodulin-Dependent Protein Kinase II Triggers Atrial Fibrillation
- Creators
- Anil Purohit - From the Department of Internal Medicine, Division of Cardiovascular Medicine and Cardiovascular Research Center, Carver College of Medicine (A.P., A.G.R., X.G., B.C., O.M.K., Z.G., E.D.L., H.S., A.C.B., R.N.E.-A., P.D.S., R.M.W., L.-S.S., M.E.A.), Department of Obstetrics and Gynecology (B.Y.), and Department of Molecular Physiology and Biophysics (M.E.A.), University of Iowa, Iowa City; Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany, and Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., D.D.); Cardiology and Pneumology, German Heart Center, University Hospital Goettingen, Goettingen, Germany (S.N., T.S., L.S.M.); and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX (N.L., X.H.T.W.)Adam RokitaXiaoqun GuanBiyi ChenOlha KovalNiels VoigtStefan NeefThomas SowaZhan GaoElizabeth LuczakHrafnhildur StefansdottirAndrew BehuninNa LiRamzi El-AccaouiBaoli YangPaari SwaminathanRobert WeissXander WehrensLong-Sheng SongDobromir DobrevLars MaierMark Anderson
- Resource Type
- Journal article
- Publication Details
- Circulation (New York, N.Y.), Vol.128(16), pp.1748-1757
- DOI
- 10.1161/CIRCULATIONAHA.113.003313
- PMID
- 24030498
- NLM abbreviation
- Circulation
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Publisher
- Lippincott Williams & Wilkins
- Language
- English
- Date published
- 10/15/2013
- Academic Unit
- Radiology; Cardiovascular Medicine; BioVentures Center; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984094395602771
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