| Downregulation of connexin40 and increased prevalence of atrial arrhythmias in transgenic mice with cardiac-restricted overexpression of tumor necrosis factor. | |
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MedLine Citation:
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PMID: 17122196 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Atrial arrhythmias, primarily atrial fibrillation, have been independently associated with structural remodeling and with inflammation. We hypothesized that sustained inflammatory signaling by tumor necrosis factor (TNF) would lead to alterations both in underlying atrial myocardial structure and in atrial electrical conduction. We performed ECG recording, intracardiac electrophysiology studies, epicardial mapping, and connexin immunohistochemical analyses on transgenic mice with targeted overexpression of TNF in the cardiac compartment (MHCsTNF) and on wild-type (WT) control mice (age 8-16 wk). Atrial and ventricular conduction abnormalities were always evident on ECG in MHCsTNF mice, including a shortened atrioventricular interval with a wide QRS duration secondary to junctional rhythm. Supraventricular arrhythmias were observed in five of eight MHCsTNF mice, whereas none of the mice demonstrated ventricular arrhythmias. No arrhythmias were observed in WT mice. Left ventricular conduction velocity during apical pacing was similar between the two mouse groups. Connexin40 was significantly downregulated in MHCsTNF mice. In contrast, connexin43 density was not significantly altered in MHCsTNF mice, but rather dispersed away from the intercalated disks. In conclusion, sustained inflammatory signaling contributed to atrial structural remodeling and downregulation of connexin40 that was associated with an increased prevalence of atrial arrhythmias. |
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Authors:
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Sam E Sawaya; Yadavendra S Rajawat; Tapan G Rami; Gabor Szalai; Robert L Price; Natarajan Sivasubramanian; Douglas L Mann; Dirar S Khoury |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2006-11-22 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 292 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2007 Mar |
Date Detail:
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Created Date: 2007-03-06 Completed Date: 2007-04-26 Revised Date: 2007-12-03 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H1561-7 Citation Subset: IM |
Affiliation:
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Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Atrial Fibrillation / physiopathology* Connexins / genetics* Electrocardiography Gene Expression Regulation* Heart / physiopathology Mice Mice, Inbred C57BL Mice, Inbred ICR Mice, Transgenic Tumor Necrosis Factor-alpha / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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HL-42250-10/10/HL/NHLBI NIH HHS; P50-HL-06H/HL/NHLBI NIH HHS; R01-HL-58081-01/HL/NHLBI NIH HHS; R01-HL-61543-01/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Connexins; 0/Tumor Necrosis Factor-alpha; 0/connexin 40 |
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